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1
Pathania, Anup Singh. „Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges“. Cancers 16, Nr. 12 (12.06.2024): 2201. http://dx.doi.org/10.3390/cancers16122201.
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The tumor immune microenvironment is pivotal in cancer initiation, advancement, and regulation. Its molecular and cellular composition is critical throughout the disease, as it can influence the balance between suppressive and cytotoxic immune responses within the tumor’s vicinity. Studies on the tumor immune microenvironment have enriched our understanding of the intricate interplay between tumors and their immunological surroundings in various human cancers. These studies illuminate the role of significant components of the immune microenvironment, which have not been extensively explored in pediatric tumors before and may influence the responsiveness or resistance to therapeutic agents. Our deepening understanding of the pediatric tumor immune microenvironment is helping to overcome challenges related to the effectiveness of existing therapeutic strategies, including immunotherapies. Although in the early stages, targeted therapies that modulate the tumor immune microenvironment of pediatric solid tumors hold promise for improved outcomes. Focusing on various aspects of tumor immune biology in pediatric patients presents a therapeutic opportunity that could improve treatment outcomes. This review offers a comprehensive examination of recent literature concerning profiling the immune microenvironment in various pediatric tumors. It seeks to condense research findings on characterizing the immune microenvironment in pediatric tumors and its impact on tumor development, metastasis, and response to therapeutic modalities. It covers the immune microenvironment’s role in tumor development, interactions with tumor cells, and its impact on the tumor’s response to immunotherapy. The review also discusses challenges targeting the immune microenvironment for pediatric cancer therapies.
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Tillyashaykhov, Mirzagaleb, Elena Boyko und Shakhnoza Jumaniyazova. „EXTRATUMOR MICROENVIRONMENT IN RENAL CELL CARCINOMA“. UZBEK MEDICAL JOURNAL 2, Nr. 4 (30.04.2021): 5–12. http://dx.doi.org/10.26739/2181-0664-2021-4-1.
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The review is focused on studying the immunosuppressive mechanisms acting in the microenvironment of renal cell carcinoma tumors. The report contains a collection of basic literature materials on the study of tumor growth factors that boost tumor cell proliferation and metastasis. The tumor microenvironment (TME) limits the immune surveillance of tumor-associated antigens and the effectiveness of immune checkpoint inhibitors. Although renal cell carcinoma is one of several tumor types sensitive to immune checkpoint inhibitors, the efficacy of these agents is likely to be limited by different tumor-infiltrating myeloid cells of bone marrow that make up the TME. Several strategies aimed at eliminating the onset of these cells in tumor tissue or neutralizing their immunosuppressive function have shown encouraging results in animal tumor models and clinical trials.Keywords: cytotoxic T lymphocytes (CTL), immune checkpoint inhibitor (ICI), tumor microenvironment (MEV), myeloid-derived suppressor cells (MDSC), regulatory T cells (Tregs), renal cell carcinoma (RCC), tumor-associated macrophages (TAM), vascular endothelial growth factor (VEGF)
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Chew, Valerie, Han Chong Toh und Jean-Pierre Abastado. „Immune Microenvironment in Tumor Progression: Characteristics and Challenges for Therapy“. Journal of Oncology 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/608406.
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The tumor microenvironment plays a critical role in cancer development, progression, and control. The molecular and cellular nature of the tumor immune microenvironment influences disease outcome by altering the balance of suppressive versus cytotoxic responses in the vicinity of the tumor. Recent developments in systems biology have improved our understanding of the complex interactions between tumors and their immunological microenvironment in various human cancers. Effective tumor surveillance by the host immune system protects against disease, but chronic inflammation and tumor “immunoediting” have also been implicated in disease development and progression. Accordingly, reactivation and maintenance of appropriate antitumor responses within the tumor microenvironment correlate with a good prognosis in cancer patients. Improved understanding of the factors that shape the tumor microenvironment will be critical for the development of effective future strategies for disease management. The manipulation of these microenvironmental factors is already emerging as a promising tool for novel cancer treatments. In this paper, we summarize the various roles of the tumor microenvironment in cancer, focusing on immunological mediators of tumor progression and control, as well as the significant challenges for future therapies.
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SK, Deshmukh. „Immune Cells in the Tumor Microenvironment and Cancer Stem Cells: Interplay for Tumor Progression“. Journal of Embryology & Stem Cell Research 2, Nr. 2 (2018): 1–2. http://dx.doi.org/10.23880/jes-16000109.
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5
Meo, Concetta, und Filomena de Nigris. „Clinical Potential of YY1-Hypoxia Axis for Vascular Normalization and to Improve Immunotherapy“. Cancers 16, Nr. 3 (23.01.2024): 491. http://dx.doi.org/10.3390/cancers16030491.
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Abnormal vasculature in solid tumors causes poor blood perfusion, hypoxia, low pH, and immune evasion. It also shapes the tumor microenvironment and affects response to immunotherapy. The combination of antiangiogenic therapy and immunotherapy has emerged as a promising approach to normalize vasculature and unlock the full potential of immunotherapy. However, the unpredictable and redundant mechanisms of vascularization and immune suppression triggered by tumor-specific hypoxic microenvironments indicate that such combination therapies need to be further evaluated to improve patient outcomes. Here, we provide an overview of the interplay between tumor angiogenesis and immune modulation and review the function and mechanism of the YY1-HIF axis that regulates the vascular and immune tumor microenvironment. Furthermore, we discuss the potential of targeting YY1 and other strategies, such as nanocarrier delivery systems and engineered immune cells (CAR-T), to normalize tumor vascularization and re-establish an immune-permissive microenvironment to enhance the efficacy of cancer therapy.
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Kang, Minjeong, DaeYong Lee, Yifan Wang, Betty Kim und Wen Jiang. „Abstract 3230: Tumor microenvironment modulation by immunotherapy sensitizes solid tumors to radiation“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 3230. http://dx.doi.org/10.1158/1538-7445.am2023-3230.
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Abstract Radiation therapy (RT) has been prevalently implemented to treat cancer in clinical settings by inducing DNA damage in tumor cells. However, tumor microenvironmental factors such as severe hypoxic conditions and vascular anomalies attenuate the therapeutic efficacy of RT, thus resulting in unsatisfactory outcomes in solid tumors. Recently, Immune checkpoint blockade (ICB) has improved immune recognition to tumor cells and normalized tumor vasculature to diminish hypoxia in solid tumors. Herein, we suggest that RT combined with ICB synergistically alters tumor microenvironments, thus facilitating the recruitment of cytotoxic immune cells into tumors as well as sensitizing radiation effectiveness. RT in combination with ICB not only normalized tumor vasculature to reduce hypoxia, but also increased anti-tumor effects from immune-mediated toxicity and DNA damage-mediated apoptosis in several solid tumor-bearing mouse models to a greater extent than did either monotreatment of RT or ICB. This study will provide mechanistic insight into synergistic effects conferred by RT and ICB as well as a strong preclinical rationale for combining the two therapeutic modalities in human cancers. Citation Format: Minjeong Kang, DaeYong Lee, Yifan Wang, Betty Kim, Wen Jiang. Tumor microenvironment modulation by immunotherapy sensitizes solid tumors to radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3230.
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Gao, Zetian, Qiubo Zhang, Xie Zhang und Yufei Song. „Advance of T regulatory cells in tumor microenvironment remodeling and immunotherapy in pancreatic cancer“. European Journal of Inflammation 20 (Januar 2022): 1721727X2210929. http://dx.doi.org/10.1177/1721727x221092900.
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Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive, deadly, and is rarely diagnosed early. Regulatory T cells (Treg) are a multifunctional class of immunosuppressive T cells that help maintain immunologic homeostasis and participate in autoimmune diseases, transplants, and tumors. This cell type mediates immune homeostasis, tolerance, and surveillance and is associated with poor outcomes in PDAC. Tregs remodel the tumor immune microenvironment, mediate tumor immune escape, and promote tumor invasion and metastasis. A promising area of research involves regulating Tregs to reduce their infiltration into tumor tissues. However, the complexity of the immune microenvironment has limited the efficacy of immunotherapy in PDAC. Treg modulation combined with other treatments is emerging. This review summarizes the mechanisms of Tregs activity in tumor immune microenvironments in PDAC and the latest developments in immunotherapy and clinical trials.
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Noman, Muhammad Zaeem, Meriem Hasmim, Yosra Messai, Stéphane Terry, Claudine Kieda, Bassam Janji und Salem Chouaib. „Hypoxia: a key player in antitumor immune response. A Review in the Theme: Cellular Responses to Hypoxia“. American Journal of Physiology-Cell Physiology 309, Nr. 9 (01.11.2015): C569—C579. http://dx.doi.org/10.1152/ajpcell.00207.2015.
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The tumor microenvironment is a complex system, playing an important role in tumor development and progression. Besides cellular stromal components, extracellular matrix fibers, cytokines, and other metabolic mediators are also involved. In this review we outline the potential role of hypoxia, a major feature of most solid tumors, within the tumor microenvironment and how it contributes to immune resistance and immune suppression/tolerance and can be detrimental to antitumor effector cell functions. We also outline how hypoxic stress influences immunosuppressive pathways involving macrophages, myeloid-derived suppressor cells, T regulatory cells, and immune checkpoints and how it may confer tumor resistance. Finally, we discuss how microenvironmental hypoxia poses both obstacles and opportunities for new therapeutic immune interventions.
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Ahmad, Aamir. „Tumor microenvironment and immune surveillance“. Microenvironment and Microecology Research 4, Nr. 1 (2022): 6. http://dx.doi.org/10.53388/mmr2022006.
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Ferrone, Soldano, und Theresa L. Whiteside. „Tumor Microenvironment and Immune Escape“. Surgical Oncology Clinics of North America 16, Nr. 4 (Oktober 2007): 755–74. http://dx.doi.org/10.1016/j.soc.2007.08.004.
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Cunha, Lucas Leite, Marjory Alana Marcello und Laura Sterian Ward. „The role of the inflammatory microenvironment in thyroid carcinogenesis“. Endocrine-Related Cancer 21, Nr. 3 (03.12.2013): R85—R103. http://dx.doi.org/10.1530/erc-13-0431.
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Immune responses against thyroid carcinomas have long been demonstrated and associations between inflammatory microenvironment and thyroid carcinomas repeatedly reported. This scenario has prompted scientists throughout the world to unveil how the inflammatory microenvironment is established in thyroid tumors and what is its influence on the outcome of patients with thyroid carcinoma. Many studies have reported the role of evasion from the immune system in tumor progression and reinforced the weakness of the innate immune response toward thyroid cancer spread in advanced stages. Translational studies have provided evidence that an increased density of tumor-associated macrophages in poorly differentiated thyroid carcinoma (DTC) is associated with an aggressive phenotype at diagnosis and decreased cancer-related survival, whereas well-DTC microenvironment enriched with macrophages is correlated with improved disease-free survival. It is possible that these different results are related to different microenvironments. Several studies have provided evidence that patients whose tumors are not infiltrated by lymphocytes present a high recurrence rate, suggesting that the presence of lymphocytes in the tumor microenvironment may favor the prognosis of patients with thyroid carcinoma. However, the effect of lymphocytes and other immune cells on patient outcome seems to result from complex interactions between the tumor and immune system, and the molecular pattern of cytokines and chemokines helps to explain the involvement of the immune system in thyroid tumor progression. The inflammatory microenvironment may help to characterize aggressive tumors and to identify patients who would benefit from a more invasive approach, probably sparing the vast majority of patients with an indolent disease from unnecessary procedures.
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Nelson, Delia, Scott Fisher und Bruce Robinson. „The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment“. Journal of Immunology Research 2014 (2014): 1–14. http://dx.doi.org/10.1155/2014/789069.
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Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient “dangerous” tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients.
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Ye, Jiaan, Longgang Cui, Xiaochen Zhao und Guanghui Lan. „Comparing of pan-cancer tumor immune microenvironment.“ Journal of Clinical Oncology 39, Nr. 15_suppl (20.05.2021): e15100-e15100. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e15100.
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e15100 Background: Cancer treatment has entered the era of immune checkpoint inhibitors (ICI), but different tumors have different responses to ICI drugs. For example, non-small cell lung cancer and melanoma have higher response rates to ICIs than colorectal cancer and liver cancer patients. Previous studies have shown that tumor immune microenvironment have a great impact on the efficacy of ICI. Methods: This study retrospectively included pan-cancer patient specimens, using multiple fluorescent labeling immunohistochemistry to explore the differences in the immune microenvironment of different tumors. Shapiro-Wilk was used for normality test, and ANOVA or Kruskal Wallis test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 308 patients, including 119 (38.6%) NSCLC patients, 72 (23.4%) Colorectal cancer patients, 51 (16.6%) Hepatobiliary cancer patients and 66 (21.4%) Others types of cancer patients. Among them, there was 192 (62.3%) Male, and 116 (37.7%) Female, and the median age was 57 (50-66). The proportion of CD8+ T cells and natural killer cell in tumor was statistically different. The proportion of CD8+ T cells in NSCLC, Colorectal cancer, Hepatobiliary cancer and others was 2.16%, 1%, 1.77% and 2.63%, p < 0.01; the proportion of natural killer cell was 16.44 %, 4.91%, 5.58% and 3.29%, p < 0.01. Conclusions: Different tumor types have different immune microenvironments. These results may provide valuable clues for future ICI trail design.
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Chen, Anna, Ines Neuwirth und Dietmar Herndler-Brandstetter. „Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice“. Cancers 15, Nr. 11 (30.05.2023): 2989. http://dx.doi.org/10.3390/cancers15112989.
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Cancer immunotherapy has brought significant clinical benefits to numerous patients with malignant disease. However, only a fraction of patients experiences complete and durable responses to currently available immunotherapies. This highlights the need for more effective immunotherapies, combination treatments and predictive biomarkers. The molecular properties of a tumor, intratumor heterogeneity and the tumor immune microenvironment decisively shape tumor evolution, metastasis and therapy resistance and are therefore key targets for precision cancer medicine. Humanized mice that support the engraftment of patient-derived tumors and recapitulate the human tumor immune microenvironment of patients represent a promising preclinical model to address fundamental questions in precision immuno-oncology and cancer immunotherapy. In this review, we provide an overview of next-generation humanized mouse models suitable for the establishment and study of patient-derived tumors. Furthermore, we discuss the opportunities and challenges of modeling the tumor immune microenvironment and testing a variety of immunotherapeutic approaches using human immune system mouse models.
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McGinity, Christopher L., Erika M. Palmieri, Veena Somasundaram, Dibyangana D. Bhattacharyya, Lisa A. Ridnour, Robert Y. S. Cheng, Aideen E. Ryan et al. „Nitric Oxide Modulates Metabolic Processes in the Tumor Immune Microenvironment“. International Journal of Molecular Sciences 22, Nr. 13 (30.06.2021): 7068. http://dx.doi.org/10.3390/ijms22137068.
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The metabolic requirements and functions of cancer and normal tissues are vastly different. Due to the rapid growth of cancer cells in the tumor microenvironment, distorted vasculature is commonly observed, which creates harsh environments that require rigorous and constantly evolving cellular adaption. A common hallmark of aggressive and therapeutically resistant tumors is hypoxia and hypoxia-induced stress markers. However, recent studies have identified alterations in a wide spectrum of metabolic pathways that dictate tumor behavior and response to therapy. Accordingly, it is becoming clear that metabolic processes are not uniform throughout the tumor microenvironment. Metabolic processes differ and are cell type specific where various factors promote metabolic heterogeneity within the tumor microenvironment. Furthermore, within the tumor, these metabolically distinct cell types can organize to form cellular neighborhoods that serve to establish a pro-tumor milieu in which distant and spatially distinct cellular neighborhoods can communicate via signaling metabolites from stroma, immune and tumor cells. In this review, we will discuss how biochemical interactions of various metabolic pathways influence cancer and immune microenvironments, as well as associated mechanisms that lead to good or poor clinical outcomes.
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Almeida-Nunes, Diana Luísa, Ana Mendes-Frias, Ricardo Silvestre, Ricardo Jorge Dinis-Oliveira und Sara Ricardo. „Immune Tumor Microenvironment in Ovarian Cancer Ascites“. International Journal of Molecular Sciences 23, Nr. 18 (14.09.2022): 10692. http://dx.doi.org/10.3390/ijms231810692.
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Ovarian cancer (OC) has a specific type of metastasis, via transcoelomic, and most of the patients are diagnosed at advanced stages with multiple tumors spread within the peritoneal cavity. The role of Malignant Ascites (MA) is to serve as a transporter of tumor cells from the primary location to the peritoneal wall or to the surface of the peritoneal organs. MA comprise cellular components with tumor and non-tumor cells and acellular components, creating a unique microenvironment capable of modifying the tumor behavior. These microenvironment factors influence tumor cell proliferation, progression, chemoresistance, and immune evasion, suggesting that MA play an active role in OC progression. Tumor cells induce a complex immune suppression that neutralizes antitumor immunity, leading to disease progression and treatment failure, provoking a tumor-promoting environment. In this review, we will focus on the High-Grade Serous Carcinoma (HGSC) microenvironment with special attention to the tumor microenvironment immunology.
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Kalkusova, Katerina, Sindija Smite, Elea Darras, Pavla Taborska, Dmitry Stakheev, Luca Vannucci, Jirina Bartunkova und Daniel Smrz. „Mast Cells and Dendritic Cells as Cellular Immune Checkpoints in Immunotherapy of Solid Tumors“. International Journal of Molecular Sciences 23, Nr. 19 (21.09.2022): 11080. http://dx.doi.org/10.3390/ijms231911080.
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The immune checkpoint inhibitors have revolutionized cancer immunotherapy. These inhibitors are game changers in many cancers and for many patients, sometimes show unprecedented therapeutic efficacy. However, their therapeutic efficacy is largely limited in many solid tumors where the tumor-controlled immune microenvironment prevents the immune system from efficiently reaching, recognizing, and eliminating cancer cells. The tumor immune microenvironment is largely orchestrated by immune cells through which tumors gain resistance against the immune system. Among these cells are mast cells and dendritic cells. Both cell types possess enormous capabilities to shape the immune microenvironment. These capabilities stage these cells as cellular checkpoints in the immune microenvironment. Regaining control over these cells in the tumor microenvironment can open new avenues for breaking the resistance of solid tumors to immunotherapy. In this review, we will discuss mast cells and dendritic cells in the context of solid tumors and how these immune cells can, alone or in cooperation, modulate the solid tumor resistance to the immune system. We will also discuss how this modulation could be used in novel immunotherapeutic modalities to weaken the solid tumor resistance to the immune system. This weakening could then help other immunotherapeutic modalities engage against these tumors more efficiently.
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Miyazaki, Tsubasa, Eiichi Ishikawa, Narushi Sugii und Masahide Matsuda. „Therapeutic Strategies for Overcoming Immunotherapy Resistance Mediated by Immunosuppressive Factors of the Glioblastoma Microenvironment“. Cancers 12, Nr. 7 (19.07.2020): 1960. http://dx.doi.org/10.3390/cancers12071960.
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Various mechanisms of treatment resistance have been reported for glioblastoma (GBM) and other tumors. Resistance to immunotherapy in GBM patients may be caused by acquisition of immunosuppressive ability by tumor cells and an altered tumor microenvironment. Although novel strategies using an immune-checkpoint inhibitor (ICI), such as anti-programmed cell death-1 antibody, have been clinically proven to be effective in many types of malignant tumors, such strategies may be insufficient to prevent regrowth in recurrent GBM. The main cause of GBM recurrence may be the existence of an immunosuppressive tumor microenvironment involving immunosuppressive cytokines, extracellular vesicles, chemokines produced by glioma and glioma-initiating cells, immunosuppressive cells, etc. Among these, recent research has paid attention to various immunosuppressive cells—including M2-type macrophages and myeloid-derived suppressor cells—that cause immunosuppression in GBM microenvironments. Here, we review the epidemiological features, tumor immune microenvironment, and associations between the expression of immune checkpoint molecules and the prognosis of GBM. We also reviewed various ongoing or future immunotherapies for GBM. Various strategies, such as a combination of ICI therapies, might overcome these immunosuppressive mechanisms in the GBM microenvironment.
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Peura, Aino, Rita Turpin, Maria Salmela, Ruixian Liu, Piia Mikkonen, Juha Klefström und Pauliina M. Munne. „Abstract B036: Micromechanical regulation of tumor immune microenvironment“. Cancer Research 84, Nr. 3_Supplement_1 (01.02.2024): B036. http://dx.doi.org/10.1158/1538-7445.advbc23-b036.
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Abstract Although the prognosis of primary breast cancer (BC) is considerably good, the prognosis of therapy-resistant, metastatic BC remains rather poor, thus being the major cause of BC-related deaths. Due to the undifferentiated and heterogenous nature of this disease, immunotherapies have been among the most promising therapeutic strategies for metastatic BC. However, in recent clinical trials, immunotherapies have had a poor success rate for breast cancer. Therefore, new therapeutic strategies and more profound knowledge of BC-specific immune-evasion mechanisms are urgently needed. We have developed a patient-derived explant model (PDEC), that allows us to cultivate patient-derived primary tumor samples. Moreover, the model also maintains alive the tumor resident immune cells, hence providing us with a unique platform for researching immunological drugs in vivo. In our model, tumor cells and tumor-derived immune cells are embedded in a 3D scaffold matrix with altering biological and physical properties. By altering the material in which the tumor cells are embedded we can also research the effect of microenvironmental factors such as stiffness and growth factors on the tumor cells. Microenvironmental stiffness is a well-known regulator of BC identity; in stiff 3D microenvironment breast cancer cells maintain their original identity, while in a softer microenvironment, they dedifferentiate towards more undifferentiated, therapy-resistant, and metastasis-mimicking subtype (Munne et al, 2021). In this study, we observed for the first time how the alterations in breast tumor microenvironmental stiffness also alter the phenotype in the breast tumor immune microenvironment concomitantly. In the soft microenvironment, the cytokine profile is polarized towards more tumor suppressing via upregulation of TGFB and downregulation of IL1B. Moreover, immune response and antigen presentation are heavily downregulated. Lastly, macrophages are depolarized from M1-like toward more tumor-promoting. This effect is induced and mediated by tumor cells and fresh immune cells embedded in similar 3D conditions that fail to secrete tumor suppressive cytokines or silence antitumor immunity. Manipulation of the tumor cell identity and tumor immune microenvironment via alteration of 3D matrices provides us a unique perspective for observing new methods of how metastatic breast cancer creates immune evasion. Moreover, the model allows us to develop novel treatments against metastatic, theraphy resistant breast cancer and test them easily in ex vivo conditions. Citation Format: Aino Peura, Rita Turpin, Maria Salmela, Ruixian Liu, Piia Mikkonen, Juha Klefström, Pauliina M Munne. Micromechanical regulation of tumor immune microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B036.
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Huber, Magdalena, Corinna U. Brehm, Thomas M. Gress, Malte Buchholz, Bilal Alashkar Alhamwe, Elke von Strandmann, Emily P. Slater, Jörg W. Bartsch, Christian Bauer und Matthias Lauth. „The Immune Microenvironment in Pancreatic Cancer“. International Journal of Molecular Sciences 21, Nr. 19 (03.10.2020): 7307. http://dx.doi.org/10.3390/ijms21197307.
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The biology of solid tumors is strongly determined by the interactions of cancer cells with their surrounding microenvironment. In this regard, pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) represents a paradigmatic example for the multitude of possible tumor–stroma interactions. PDAC has proven particularly refractory to novel immunotherapies, which is a fact that is mediated by a unique assemblage of various immune cells creating a strongly immunosuppressive environment in which this cancer type thrives. In this review, we outline currently available knowledge on the cross-talk between tumor cells and the cellular immune microenvironment, highlighting the physiological and pathological cellular interactions, as well as the resulting therapeutic approaches derived thereof. Hopefully a better understanding of the complex tumor–stroma interactions will one day lead to a significant advancement in patient care.
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Swartz, Melody A. „Lymphatic Control of the Tumor Immune Microenvironment“. Blood 134, Supplement_1 (13.11.2019): SCI—46—SCI—46. http://dx.doi.org/10.1182/blood-2019-123389.
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Tumor engagement or activation of surrounding lymphatic vessels is well-known to correlate with tumor progression and metastasis in melanoma and many other cancers. We and others have identified several mechanisms by which the lymphatic growth factor VEGF-C and lymphangiogenesis can promote metastasis, including (i) increasing immune suppressive cell types and factors in the tumor microenvironment both directly and indirectly, (ii) inhibiting maturation of antigen-presenting cells and T cell activation, and (iii) driving changes in the stromal microenvironment that promote both cancer invasion and immune suppression. However, lymphatic activation also enhances communication with cells in the draining lymph node by antigen and cell transport, which may trigger the initiation of adaptive immune responses against the tumor. Under normal conditions, the potential anti-tumor effects are rendered 'dormant' by the pro-tumor immune suppression, and the tumor progresses. However, we are now observing that lymphangiogenic tumors are exceptionally responsive to immunotherapy, implying that the anti-tumor aspects can be unleashed when the overall balance of pro- and anti-tumor immune aspects is tipped enough towards the latter (e.g., upon tumor cell killing). On the mechanistic side, we are finding that 'lymphangiogenic potentiation' depends on tumor cell infiltration of both CD103+ dendritic cells and naïve T cells, driving local T cell education post-immunotherapy and antigen spreading. On the translational side, we are developing novel strategies to exploit lymphangiogenesis for cancer immunotherapy. Understanding the yin and yang of lymphatic activation in the tumor microenvironment and how it affects immunity may lead to exciting new translational strategies for cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.
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Zhou, Chengzhi, Yanhui Chen, Ying Hu, Yang Liu und Henghui Zhang. „The cross talk between the molecular alterations and tumor immunity in the microenvironment in non-small-cell lung carcinoma.“ Journal of Clinical Oncology 37, Nr. 15_suppl (20.05.2019): e20043-e20043. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e20043.
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e20043 Background: The previous study indicated that the biomarkers of molecular alterations and tumor immunity in the microenvironment could predict the response of immunotherapy in NSCLC patients. However, the cross talk between the two factors is unclear. This study was designed to investigated the features of tumor immunity in the microenvironment of deferential molecular characterization in NSCLC patients. Methods: Tumor tissue and matched blood samples from 62 patients with NSCLC were collected. The mutation profiles were sequenced by a cancer gene-targeted NGS panel. The PD-L1 expression and immune cells infiltrated in tumor microenvironment were detected by multiplex immunofluorescence staining. Results: The distinct of molecular alterations showed the different tumor microenvironments in terms of immune cell composition and of PD-L1 expression by tumor cells in NSCLC. KRAS-mutated tumors were characterized by higher level of PD-L1 expression and lower NK cells infiltrated in tumor area than KRAS-wild type tumor. TP53-mutated tumors were characterized by higher CD8+T cell and lower NK cells infiltrated in tumor area. In contrast, EGFR-mutated tumors were characterized by lower level of PD-L1 expression and higher NK cells. Moreover, we found that the PD-L1 expression increased in MET gene CNV gain tumors than MET wild type tumors. Conclusions: The features of tumor immunity in the microenvironment changed in deferential molecular characterization in NSCLC. it may help to explain the phenomenon that the efficacy of immunotherapy changed in deferential molecular characterization of NSCLC.
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Otterlei Fjørtoft, Marit, Kanutte Huse und Inga Hansine Rye. „The Tumor Immune Microenvironment in Breast Cancer Progression“. Acta Oncologica 63 (23.05.2024): 359–67. http://dx.doi.org/10.2340/1651-226x.2024.33008.
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Background: The tumor microenvironment significantly influences breast cancer development, progression, and metastasis. Various immune cell populations, including T cells, B cells, NK cells, and myeloid cells exhibit diverse functions in different breast cancer subtypes, contributing to both anti-tumor and pro-tumor activities. Purpose: This review provides an overview of the predominant immune cell populations in breast cancer subtypes, elucidating their suppressive and prognostic effects. We aim to outline the role of the immune microenvironment from normal breast tissue to invasive cancer and distant metastasis. Methods: A comprehensive literature review was conducted to analyze the involvement of immune cells throughout breast cancer progression. Results: In breast cancer, tumors exhibit increased immune cell infiltration compared to normal tissue. Variations exist across subtypes, with higher levels observed in triple-negative and HER2+ tumors are linked to better survival. In contrast, ER+ tumors display lower immune infiltration, associated with poorer outcomes. Furthermore, metastatic sites commonly exhibit a more immunosuppressive microenvironment. Conclusion: Understanding the complex interaction between tumor and immune cells during breast cancer progression is essential for future research and the development of immune-based strategies. This comprehensive understanding may pave the way for more effective treatment approaches and improved patients outcomes.
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Tsunokake, Junichi, Fumiyoshi Fujishima, Hirofumi Watanabe, Ikuro Sato, Koh Miura, Kazuhiro Sakamoto, Hiroyoshi Suzuki et al. „Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment“. Cancers 14, Nr. 9 (26.04.2022): 2152. http://dx.doi.org/10.3390/cancers14092152.
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The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.
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Tsunokake, Junichi, Fumiyoshi Fujishima, Hirofumi Watanabe, Ikuro Sato, Koh Miura, Kazuhiro Sakamoto, Hiroyoshi Suzuki et al. „Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment“. Cancers 14, Nr. 9 (26.04.2022): 2152. http://dx.doi.org/10.3390/cancers14092152.
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The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.
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Tsunokake, Junichi, Fumiyoshi Fujishima, Hirofumi Watanabe, Ikuro Sato, Koh Miura, Kazuhiro Sakamoto, Hiroyoshi Suzuki et al. „Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment“. Cancers 14, Nr. 9 (26.04.2022): 2152. http://dx.doi.org/10.3390/cancers14092152.
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The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.
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Steidl, Christian. „The Role of the Tumor Microenvironment in Lymphoid Malignancies“. Blood 126, Nr. 23 (03.12.2015): SCI—46—SCI—46. http://dx.doi.org/10.1182/blood.v126.23.sci-46.sci-46.
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Lymphoid cancers represent a heterogeneous group of neoplasms composed of malignant lymphoid cells with variable infiltration by non-neoplastic, mostly immune cells (tumor microenvironment). For some subtypes of lymphoid cancers, the contribution of the microenvironment to the histological appearance is widely recognized and used for pathological classification. Although microenvironment-related biology in lymphoid cancers has been primarily explored in a core set of lymphoma subtypes, the number of entities studied has recently accelerated. The pathogenic evolution of tumor microenvironments and in particular their composition and spatial distribution can be perceived as a complex function of 1) genetic alterations within the malignant cell population, 2) the extent and dependence on the molecular crosstalk involving cyto- and chemokines, and 3) host-specific factors. As a result, three major patterns of microenvironmental architecture can be distinguished termed "Re-education", "Recruitment" and "Effacement". Hodgkin lymphoma can serve as a paradigm for an extensive crosstalk between tumor cells and a quantitatively dominant tumor microenvironment. Importantly, related prognostic implications of tumor microenvironment composition (e.g. macrophage content, representation of T cell subsets) have been extensively studied in this disease. With focus on B cell lymphomas, this talk will highlight the emerging literature about genetic alterations in malignant lymphoma cells that provide the foundation for somatically acquired immune privilege and evasion from immune surveillance. The genomic changes discussed in this talk can be broadly categorized according to the effect that they exert on the tumor microenvironment: 1) Loss or down-regulation of (surface) molecules leading to decreased immunogenicity of tumor cells (e.g. mutations of B2M, CIITA); 2) Increased expression of surface molecules suppressing immune cell function (e.g. structural genomic changes of PDL1, PDL2); 3) Recruitment or induction of a regulatory cellular milieu (e.g. mutations in JAK-STAT and NFκB signaling pathways). The discovery of gene mutations underlying immune privilege, properties of the altered molecules, downstream functional consequences and clinical rationales for therapeutic intervention will be presented in the context of specific lymphoma subtypes. It will be discussed how precise description of genomic and molecular alterations underlying immune privilege might accelerate effective targeting of microenvironment-related biology in the clinical setting. Moreover, the development and clinical implementation of predictive biomarkers will be outlined that harbor the potential to inform on companion diagnostic approaches to accompany therapies such as immunological checkpoint inhibition. Disclosures No relevant conflicts of interest to declare.
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Tzeng, Hong-Tai, und Yu-Jie Huang. „Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity“. International Journal of Molecular Sciences 24, Nr. 5 (23.02.2023): 4422. http://dx.doi.org/10.3390/ijms24054422.
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Tumor vasculature abnormality creates a microenvironment that is not suitable for anti-tumor immune response and thereby induces resistance to immunotherapy. Remodeling of dysfunctional tumor blood vessels by anti-angiogenic approaches, known as vascular normalization, reshapes the tumor microenvironment toward an immune-favorable one and improves the effectiveness of immunotherapy. The tumor vasculature serves as a potential pharmacological target with the capacity of promoting an anti-tumor immune response. In this review, the molecular mechanisms involved in tumor vascular microenvironment-modulated immune reactions are summarized. In addition, the evidence of pre-clinical and clinical studies for the combined targeting of pro-angiogenic signaling and immune checkpoint molecules with therapeutic potential are highlighted. The heterogeneity of endothelial cells in tumors that regulate tissue-specific immune responses is also discussed. The crosstalk between tumor endothelial cells and immune cells in individual tissues is postulated to have a unique molecular signature and may be considered as a potential target for the development of new immunotherapeutic approaches.
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Selleri, Silvia, Cristiano Rumio, Marianna Sabatino, Francesco M. Marincola und Ena Wang. „Tumor Microenvironment and the Immune Response“. Surgical Oncology Clinics of North America 16, Nr. 4 (Oktober 2007): 737–53. http://dx.doi.org/10.1016/j.soc.2007.07.002.
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Toor, Salman M., Varun Sasidharan Nair, Julie Decock und Eyad Elkord. „Immune checkpoints in the tumor microenvironment“. Seminars in Cancer Biology 65 (Oktober 2020): 1–12. http://dx.doi.org/10.1016/j.semcancer.2019.06.021.
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Gajewski, Thomas F., Yuru Meng und Helena Harlin. „Immune Suppression in the Tumor Microenvironment“. Journal of Immunotherapy 29, Nr. 3 (Mai 2006): 233–40. http://dx.doi.org/10.1097/01.cji.0000199193.29048.56.
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Faiena, Izak, Daiki Ueno und Brian Shuch. „Glutamine and the Tumor Immune Microenvironment“. European Urology 75, Nr. 5 (Mai 2019): 764–65. http://dx.doi.org/10.1016/j.eururo.2019.01.015.
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Margul, Daniel, Camilla Yu und Mariam M. AlHilli. „Tumor Immune Microenvironment in Gynecologic Cancers“. Cancers 15, Nr. 15 (28.07.2023): 3849. http://dx.doi.org/10.3390/cancers15153849.
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Gynecologic cancers have varying response rates to immunotherapy due to the heterogeneity of each cancer’s molecular biology and features of the tumor immune microenvironment (TIME). This article reviews key features of the TIME and its role in the pathophysiology and treatment of ovarian, endometrial, cervical, vulvar, and vaginal cancer. Knowledge of the role of the TIME in gynecologic cancers has been rapidly developing with a large body of preclinical studies demonstrating an intricate yet dichotomous role that the immune system plays in either supporting the growth of cancer or opposing it and facilitating effective treatment. Many targets and therapeutics have been identified including cytokines, antibodies, small molecules, vaccines, adoptive cell therapy, and bacterial-based therapies but most efforts in gynecologic cancers to utilize them have not been effective. However, with the development of immune checkpoint inhibitors, we have started to see the rapid and successful employment of therapeutics in cervical and endometrial cancer. There remain many challenges in utilizing the TIME, particularly in ovarian cancer, and further studies are needed to identify and validate efficacious therapeutics.
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Huang, Yanyu, Hsiao-Chi Wang, Junwei Zhao, Ming-Heng Wu und Tsung-Chieh Shih. „Immunosuppressive Roles of Galectin-1 in the Tumor Microenvironment“. Biomolecules 11, Nr. 10 (23.09.2021): 1398. http://dx.doi.org/10.3390/biom11101398.
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Evasion of immune surveillance is an accepted hallmark of tumor progression. The production of immune suppressive mediators by tumor cells is one of the major mechanisms of tumor immune escape. Galectin-1 (Gal-1), a pivotal immunosuppressive molecule, is expressed by many types of cancer. Tumor-secreted Gal-1 can bind to glycosylated receptors on immune cells and trigger the suppression of immune cell function in the tumor microenvironment, contributing to the immune evasion of tumors. The aim of this review is to summarize the current literature on the expression and function of Gal-1 in the human tumor microenvironment, as well as therapeutics targeting Gal-1.
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Tian, Linjie, M. Ines Pascoal Ramos, Emma de Ruiter, Ana Paucarmayta, Eline Elshof, Stefan Willems, Chang Song et al. „694 NC410 is a novel immunomedicine for the treatment of solid tumors“. Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A736. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0694.
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BackgroundAbnormalities in the extracellular matrix of tumor microenvironments support tumor progression, lead to immune dysfunction, and provide a target for cancer therapeutics. Collagens are a primary component of the extracellular matrix. Abnormal levels of collagen and of the collagen-domain containing complement component 1q (C1q) in tumor microenvironments has been proposed to disrupt anti-tumor immunity. LAIR-1 is an adhesion molecule and inhibitory receptor expressed on the cell surface of several immune cell subsets. LAIR-1 binding to collagen-like domains present in collagens and C1q inhibit immune cell function. LAIR-2 is a soluble homolog of LAIR-1 that binds to and outcompetes LAIR-1 binding to collagens and C1q and serves as a natural decoy to promote immune function.MethodsTaking advantage of a natural decoy system, we designed a protein biologic, NC410, composed of LAIR-2 fused with a functional IgG1 Fc domain to target collagen-rich tumors and promote immune activation, infiltration and effector function.ResultsNC410 has increased avidity due to Fc mediated dimerization, and blocks LAIR-1 interactions with ligands, and LAIR-1 signaling. In vivo administration of NC410 in humanized tumor models reduced tumor growth in a dose dependent fashion. NC410 increased the numbers of infiltrating human CD8+ and CD4+ T cells in the tumor, which is associated with increased levels of chemokines in the local tumor environment. Effector function was also enhanced, as denoted by increased levels of IFN-gamma and Granzyme B in the local tumor environment. In addition, NC410 increased specific collagen degradative products in the serum of humanized tumor-bearing mice, suggesting NC410 may promote tumor microenvironment remodeling and immune accessibility to further promote anti-tumor immunity.ConclusionsThese data support NC410 as a novel therapeutic for targeting collagen-rich tumors and enabling normalization of the tumor-immune microenvironment. FIH studies have recently been initiated with NC410.
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Ogiya, Rin, Naoki Niikura, Nobue Kumaki, Hiroyuki Yasojima, Tsutomu Iwasa, Chizuko Kanbayashi, Risa Oshitanai et al. „Immune microenvironment in brain metastases of breast cancer.“ Journal of Clinical Oncology 35, Nr. 15_suppl (20.05.2017): 1081. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.1081.
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1081 Background: In patients with brain metastasis (BM) of melanoma or lung cancer, significant activity of immune checkpoint inhibitors has been reported. However, details of the immune microenvironment in BM has not been unveiled. In this study, we used immunohistochemistry (IHC) to compare primary breast tumors and BM tumor samples with respect to tumor infiltrating lymphocytes (TILs) and tumor characteristics related to the immune system. Methods: We retrospectively identified 107 patients with breast cancer, diagnosed with BM, who had undergone surgery between 2001 and 2012 at 8 institutions. We collected 191 samples which included both BM samples alone and pair-matched samples (primary and BM). Hematoxylin and eosin (H&E) stained slides were evaluated for stromal TILs in 10% increments (0–1%, > 1– < 10%, 10%–100%). IHC was performed using the following primary antibodies: CD4, CD8, Foxp3, PD-L1, PD-L2 and HLA class I. The cells positive for each antibody signal were counted automatically using ImageJ (NIH). The expression of PD-L1, PD-L2, and HLA on the tumor cells was scored as 0 (negative), 1 (weak or focal), or 2 (strong). Results: The median category of TILs of BM tumors was > 1– < 10% (range: 1–30%). Forty-six pair-matched samples were analyzed and the percentage of TILs in the primary breast tumor was significantly higher than that in BM samples (paired t-test, P < 0.01). The number of CD4/CD8/Foxp3 positive cells in primary breast tumor was also significantly higher than in BM samples (paired t-test, P < 0.05 for all categories). The negative/positive conversion occurred with the expression of HLA/PD-L2 on tumor cells (paired t-test, P = 0.03/0.06, respectively). No significant difference was observed in the overall survival (OS) of patients, from initial BM, based on high or low TILs (log-rank test, P = 0.131). However, triple negative breast cancer patients with low TILs had significantly shorter OS compared with patients with high TILs (log-rank test, P = 0.04). Conclusions: We demonstrated that TILs in BM tumors was significantly lower as compared to primary breast tumors. The expression of immune related molecules on tumor cells was converted in BM tumors.
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Nie, Jeffrey Z., Man-Tzu Wang und Daotai Nie. „Regulations of Tumor Microenvironment by Prostaglandins“. Cancers 15, Nr. 12 (07.06.2023): 3090. http://dx.doi.org/10.3390/cancers15123090.
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Prostaglandins, the bioactive lipids generated from the metabolism of arachidonic acid through cyclooxygenases, have potent effects on many constituents of tumor microenvironments. In this review, we will describe the formation and activities of prostaglandins in the context of the tumor microenvironment. We will discuss the regulation of cancer-associated fibroblasts and immune constituents by prostaglandins and their roles in immune escapes during tumor progression. The review concludes with future perspectives on improving the efficacy of immunotherapy through repurposing non-steroid anti-inflammatory drugs and other prostaglandin modulators.
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Xu, Shuaishuai, Chanqi Ye, Ruyin Chen, Qiong Li und Jian Ruan. „The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms“. Cancers 14, Nr. 12 (13.06.2022): 2911. http://dx.doi.org/10.3390/cancers14122911.
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Gastroenteropancreatic neuroendocrine neoplasms feature high heterogeneity. Neuroendocrine tumor cells are closely associated with the tumor microenvironment. Tumor-infiltrating immune cells are mutually educated by each other and by tumor cells. Immune cells have dual protumorigenic and antitumorigenic effects. The immune environment is conducive to the invasion and metastasis of the tumor; in turn, tumor cells can change the immune environment. These cells also form cytokines, immune checkpoint systems, and tertiary lymphoid structures to participate in the process of mutual adaptation. Additionally, the fibroblasts, vascular structure, and microbiota exhibit interactions with tumor cells. From bench to bedside, clinical practice related to the tumor microenvironment is also regarded as promising. Targeting immune components and angiogenic regulatory molecules has been shown to be effective. The clinical efficacy of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses remains to be further discussed in clinical trials. Moreover, combination therapy is feasible for advanced high-grade tumors. The regulation of the tumor microenvironment based on multiple omics results can suggest innovative therapeutic strategies to prevent tumors from succeeding in immune escape and to support antitumoral effects.
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Bao, Zhaoshi, Ying Zhang, Peng Wang, Chengjun Zheng, Zhiliang Wang und Wenhua Fan. „CSIG-12. GLIOMA MICROENVIRONMENT: FUNCTIONS, MOLECULAR MECHANISMS, AND THERAPEUTIC IMPLICATIONS“. Neuro-Oncology 25, Supplement_5 (01.11.2023): v42. http://dx.doi.org/10.1093/neuonc/noad179.0168.
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Abstract Abstract Gliomas are the most common intracranial tumors in adults. The high mortality and disability rates place a heavy burden on society and the families of patients. The median survival of patients who have primary grade 4 glioma at the World Health Organization is only 14.6 months. Unlike primary glioblastoma (WHO grade 4, pGBM) which usually occurs in older adults, secondary glioblastoma (WHO grade 4, sGBM) with isotrate dehydrogenase (IDH) mutations typically progresses from low to high grades within 5-10 years of diagnosis. Although surgery, radiotherapy, and chemotherapy have almost become the standard treatment for gliomas, the prognosis of patients is still poor. In recent years, the immune microenvironment has gradually become a possible direction for tumor treatment, and treatment methods such as PD1/PDL1 inhibitors and tumor vaccines have emerged. Owing to the microenvironment around the intracranial tumor cells and the body tumor being different, the microenvironment cells have their specific characteristics, and there is a blood-brain barrier, immunotherapy for the glioma microenvironment has encountered a bottleneck. Here, we summarize the current tumor-associated microenvironment and the interactions between tumor and immune cells and introduce the current status of glioma-specific microenvironment and immunotherapy for glioma. Finally, we mentioned several recent microenvironment-related research advances by our team and looked forward to future glioma microenvironmental research.
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Jang, Hochung, Eun Hye Kim, Sung-Gil Chi, Sun Hwa Kim und Yoosoo Yang. „Nanoparticles Targeting Innate Immune Cells in Tumor Microenvironment“. International Journal of Molecular Sciences 22, Nr. 18 (16.09.2021): 10009. http://dx.doi.org/10.3390/ijms221810009.
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A variety of innate immune cells such as macrophages, dendritic cells, myeloid-derived suppressor cells, natural killer cells, and neutrophils in the tumor microenvironments, contribute to tumor progression. However, while several recent reports have studied the use of immune checkpoint-based cancer immunotherapy, little work has focused on modulating the innate immune cells. This review focuses on the recent studies and challenges of using nanoparticles to target innate immune cells. In particular, we also examine the immunosuppressive properties of certain innate immune cells that limit clinical benefits. Understanding the cross-talk between tumors and innate immune cells could contribute to the development of strategies for manipulating the nanoparticles targeting tumor microenvironments.
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Chen, Houminji, Ming Li, Yanwu Guo, Yongsheng Zhong, Zhuoyi He, Yuting Xu und Junjie Zou. „Immune response in glioma’s microenvironment“. Innovative Surgical Sciences 5, Nr. 3-4 (01.09.2020): 115–25. http://dx.doi.org/10.1515/iss-2019-0001.
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Abstract Objectives Glioma is the most common tumor of the central nervous system. In this review, we outline the immunobiological factors that interact with glioma cells and tumor microenvironment (TME), providing more potential targets for clinical inhibition of glioma development and more directions for glioma treatment. Content Recent studies have shown that glioma cells secrete a variety of immune regulatory factors and interact with immune cells such as microglial cells, peripheral macrophages, myeloid-derived suppressor cells (MDSCs), and T lymphocytes in the TME. In particular, microglia plays a key role in promoting glioma growth. Infiltrating immune cells induce local production of cytokines, chemokines and growth factors. Further leads to immune escape of malignant gliomas. Summary and Outlook The complex interaction of tumor cells with the TME has largely contributed to tumor heterogeneity and poor prognosis. We review the immunobiological factors, immune cells and current immunotherapy of gliomas, provide experimental evidence for future research and treatment of gliomas.
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Crispen, Paul L., und Sergei Kusmartsev. „Mechanisms of immune evasion in bladder cancer“. Cancer Immunology, Immunotherapy 69, Nr. 1 (06.12.2019): 3–14. http://dx.doi.org/10.1007/s00262-019-02443-4.
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AbstractWith the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway). While these trials have demonstrated promising results and improvements over existing therapies, less than half of patients with advanced disease demonstrate clinical benefit from checkpoint inhibitor therapy. Recent breakthroughs in cancer biology and immunology have led to an improved understanding of the influence of the tumor microenvironment on the host’s immune system. It appears that tumors promote the formation of highly immunosuppressive microenvironments preventing generation of effective anti-tumor immune response through multiple mechanisms. Therefore, reconditioning of the tumor microenvironment and restoration of the competent immune response is essential for achieving optimal efficacy of cancer immunotherapy. In this review, we aim to discuss the major mechanisms of immune evasion in bladder cancer and highlight novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes.
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Hu, Haibei, Qiang Chen, Siqi Zheng, Shan Du, Siqin Ding und Yongzhi Lun. „Transcriptome Analysis Revealed Potential Neuro-Immune Interaction in Papillary Thyroid Carcinoma Tissues“. Diseases 11, Nr. 1 (04.01.2023): 9. http://dx.doi.org/10.3390/diseases11010009.
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Background: A recent study reported that papillary thyroid carcinoma (PTC) was associated with increased adrenergic nerve density. Meanwhile, emerging evidence suggested that tumor-innervating nerves might play a role in shaping the tumor microenvironment. We aimed to explore the potential interaction between neuronal markers and tumor microenvironmental signatures through a transcriptomic approach. Methods: mRNA sequencing was conducted using five pairs of PTC and adjacent normal tissues. The Gene Set Variation Analysis (GSVA) was performed to calculate enrichment scores of gene sets related to tumor-infiltrating immune cells and the tumor microenvironment. The potential interaction was tested using the expression levels of a series of neuronal markers and gene set enrichment scores. Results: PTC tissues were associated with increased enrichment scores of CD8 T cells, cancer-associated fibroblasts, mast cells, and checkpoint molecules. The neuronal marker for cholinergic neurons was positively correlated with CD8 T cell activation, while markers for serotonergic and dopaminergic neurons showed an inverse correlation. Conclusion: Distinct neuronal markers exerted different correlations with tumor microenvironmental signatures. Tumor-innervating nerves might play a role in the formation of the PTC microenvironment.
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Nam, Jae-Kyung, Ji-Hee Kim, Min-Sik Park, Eun Ho Kim, Joon Kim und Yoon-Jin Lee. „Radiation-Induced Fibrotic Tumor Microenvironment Regulates Anti-Tumor Immune Response“. Cancers 13, Nr. 20 (19.10.2021): 5232. http://dx.doi.org/10.3390/cancers13205232.
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High linear energy transfer (LET) radiation, such as neutron radiation, is considered more effective for the treatment of cancer than low LET radiation, such as X-rays. We previously reported that X-ray irradiation induced endothelial-to-mesenchymal transition (EndMT) and profibrotic changes, which contributed to the radioresistance of tumors. However, this effect was attenuated in tumors of endothelial-specific Trp53-knockout mice. Herein, we report that compared to X-ray irradiation, neutron radiation therapy reduced collagen deposition and suppressed EndMT in tumors. In addition to the fewer fibrotic changes, more cluster of differentiation (CD8)-positive cytotoxic T cells were observed in neutron-irradiated regrowing tumors than in X-ray-irradiated tumors. Furthermore, lower programmed death-ligand 1 (PD-L1) expression was noted in the former. Endothelial-specific Trp53 deletion suppressed fibrotic changes within the tumor environment following both X-ray and neutron radiation therapy. In particular, the upregulation in PD-L1 expression after X-ray radiation therapy was significantly dampened. Our findings suggest that compared to low LET radiation therapy, high LET radiation therapy can efficiently suppress profibrotic changes and enhance the anti-tumor immune response, resulting in delayed tumor regrowth.
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Shao, Xuejun, Shenghao Hua, Tao Feng, Dickson Kofi Wiredu Ocansey und Lei Yin. „Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion“. International Journal of Molecular Sciences 23, Nr. 19 (04.10.2022): 11789. http://dx.doi.org/10.3390/ijms231911789.
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Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial–mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies.
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Chen, Meihua, Jin Yi Lang, Tao Li, Qifeng Wang, Guangchao Xu und Shun Lu. „Antitumor effect of a whole tumor cell vaccine expressing human fibroblast activation protein in murine tumor models.“ Journal of Clinical Oncology 35, Nr. 15_suppl (20.05.2017): e14542-e14542. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14542.
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e14542 Background: Immunosuppressive factors in the tumor microenvironment reduce the therapeutic efficacy of cancer vaccines; therefore, dampening the tumor immunosuppressive environment while activating antitumor immunity should be a useful approach for cancer therapy. Cancer-associated fibroblasts (CAFs) are among the most important cellular components of the tumor microenvironment and play an important role in the development and progression of tumors. Fibroblast activation protein α (FAPα) is a type II transmembrane protein specifically expressed by CAFs in most epithelial cancers. Gene sequence homology between human and murine FAPα is 90%. Heterogeneity of genes in the evolution of the formation of such nuances can be utilized to break immune tolerance, enhance immunogenicity, induce tumour cell autoimmune responses and thus inhibit tumor growth. Methods: Tumor cells were transfected with human FAPα plasmids employing the cationic lipid DOTAP. Its antitumor effects were investigated in three established tumor models. The potential immune mechanisms were investigated through adoptive immunotherapy and 51Cr release assay. The distributions of the immune cells in the tumor microenvironment were detected by immunohistochemical staining and flow cytometry. Results: Our results shown that whole tumor cell vaccine expressing human FAPα significantly inhibit tumor growth and prolong the survival of tumor bearing mice. This antitumor immune response was involved both of cellular and humoral immune responses. FAPα specific neutralizing antibodies were found in the serum of vaccinated mice and CAFs were significantly reduced within the tumors. Furthermore, this vaccine enhanced the infiltration of CD4+ T cells and CD8+ T cells, and suppressed the accumulation of immunosuppressive cells in the tumor microenvironment. Conclusions: These findings suggest that whole tumor cell vaccine expressing human FAPα inhibit tumor growth by producing FAPα specific neutralizing antibodies and CTLs, and targeting tumor cells and CAFs. These observations provide a new strategy for the clinical use of genetically modified tumor cells as cancer vaccines.
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Xie, Shang, Xin-Yuan Zhang, Xiao-Feng Shan, Vicky Yau, Jian-Yun Zhang, Wei Wang, Yong-Pan Yan und Zhi-Gang Cai. „Hyperion Image Analysis Depicts a Preliminary Landscape of Tumor Immune Microenvironment in OSCC with Lymph Node Metastasis“. Journal of Immunology Research 2021 (21.06.2021): 1–7. http://dx.doi.org/10.1155/2021/9975423.
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Background. Oral squamous cell carcinoma (OSCC) constitutes the most common types of oral cancer. Because its prognosis varies significantly, identification of a tumor immune microenvironment could be a critical tool for treatment planning and predicting a more accurate prognosis. This study is aimed at utilizing the Hyperion imaging system to depict a preliminary landscape of the tumor immune microenvironment in OSCC with lymph node metastasis. Methods. We collected neoplasm samples from OSCC patients. Their formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained and stained utilizing a panel of 26 clinically relevant metal-conjugated antibodies. Detection and analysis were performed for these stained cells with the Hyperion imaging system. Results. Four patients met our inclusion criteria. We depicted a preliminary landscape of their tumor immune microenvironment and identified 25 distinct immune cell subsets from these OSCC patients based on phenotypic similarity. All these patients had decreased expression of CD8+ T cells in tumor specimens. Variety in cell subsets was seen, and more immune activated cells were found in patient A and patient B than those in patient C and patient D. Such differences in tumor immune microenvironments can contribute to forecasting of individual prognoses. Conclusion. The Hyperion imaging system helped to delineate a preliminary and multidimensional landscape of the tumor immune microenvironment in OSCC with lymph node metastasis and provided insights into the influence of the immune microenvironment in determination of prognoses. These results reveal possible contributory factors behind different prognoses of OSCC patients with lymph node metastasis and provide reference for individual treatment planning.
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Wang, Yuncong. „Tumor Immune Escape and Treatment“. BIO Web of Conferences 55 (2022): 01010. http://dx.doi.org/10.1051/bioconf/20225501010.
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Tumor immune escape is one of the ten characteristics of tumor occurrence and development. Immunotherapy targeting immune escape has achieved remarkable success in recent years. Immunotherapy involves many factors and links, which are related to the changes of tumor cells themselves and tumor microenvironment, and the mechanism is complex. At present, it still faces great challenges in clinical practice. This article introduces the mechanism of tumor immune escape from several aspects, including the changes of tumor itself, the changes of tumor induced microenvironment, and the tumor microenvironment promoting tumor development. At the same time, in view of these mechanisms, the current treatment strategies were sorted out, including the predicament and progress of immune checkpoint inhibitors, CAR-T therapy and immune cell therapy, aiming to clarify the ideas for the next development of tumor immunotherapy.
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Ramirez, Fabiola, Angelica Zambrano, Robert Hennis, Nathan Holland, Rajkumar Lakshmanaswamy und Jessica Chacon. „Sending a Message: Use of mRNA Vaccines to Target the Tumor Immune Microenvironment“. Vaccines 11, Nr. 9 (07.09.2023): 1465. http://dx.doi.org/10.3390/vaccines11091465.
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While cancer immunotherapies have become central to treatment, challenges associated with the ability of tumors to evade the immune system remain significant obstacles. At the heart of this issue is the tumor immune microenvironment, the complex interplay of the tumor microenvironment and the immune response. Recent advances in mRNA cancer vaccines represent major progress towards overcoming some of the challenges posed by deleterious components of the tumor immune microenvironment. Indeed, major breakthroughs in mRNA vaccine technology, such as the use of replacement nucleotides and lipid nanoparticle delivery, led to the vital success of mRNA vaccine technology in fighting COVID-19. This has in turn generated massive additional interest and investment in the platform. In this review, we detail recent research in the nature of the tumor immune microenvironment and in mRNA cancer vaccines and discuss applications by which mRNA cancer vaccines, often in combination with various adjuvants, represent major areas of potential in overcoming tumor immune microenvironment-imposed obstacles. To this end, we also review current mRNA cancer vaccine clinical trials.
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Xing, Jianlei, Jinhua Zhang und Jinyan Wang. „The Immune Regulatory Role of Adenosine in the Tumor Microenvironment“. International Journal of Molecular Sciences 24, Nr. 19 (05.10.2023): 14928. http://dx.doi.org/10.3390/ijms241914928.
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Adenosine, an immunosuppressive metabolite, is produced by adenosine triphosphate (ATP) released from dying or stressed cells and is found at high levels in the tumor microenvironment of most solid tumors. It mediates pro-tumor activities by inducing tumor cell proliferation, migration or invasion, tumor tissue angiogenesis, and chemoresistance. In addition, adenosine plays an important role in regulating anti-tumor immune responses and facilitating tumor immune escape. Adenosine receptors are broadly expressed by tumor-infiltrated immune cells, including suppressive tumor-associated macrophages and CD4+ regulatory T cells, as well as effector CD4+ T cells and CD8+ cytotoxic T lymphocytes. Therefore, adenosine is indispensable in down-regulating anti-tumor immune responses in the tumor microenvironment and contributes to tumor progression. This review describes the current progress on the role of adenosine/adenosine receptor pathway in regulating the tumor-infiltrating immune cells that contribute to tumor immune evasion and aims to provide insights into adenosine-targeted tumor immunotherapy.