Academic literature on the topic 'Exosomes, myeloid cells, tumor, PDAC'
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Journal articles on the topic "Exosomes, myeloid cells, tumor, PDAC"
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Lucotti, Serena, Yusuke Ogitani, Candia M. Kenific, Linda Bojmar, Michele Cioffi, Pernille Lauritzen, Henrik Molina, et al. "Abstract 3138: The lung pro-thrombotic niche drives cancer-associated thromboembolism via exosomal ITGB2." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3138. http://dx.doi.org/10.1158/1538-7445.am2022-3138.
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Abstract Thromboembolism (TE) is a common complication in cancer patients and the second leading cause of cancer-related deaths. The incidence of TE varies in different cancer types, with the highest risk in lung cancer and pancreatic ductal adenocarcinoma (PDAC), and in advanced-stage and metastatic cancers. Despite the benefits associated with thromboprophylaxis for symptomatic TE, the prevention of TE still remains an unmet clinical need due to lack of biomarkers predictive of TE risk and the bleeding risk associated with the routine use of anti-coagulants. Exosomes are small circulating extracellular vesicles that mediate cell-to-cell communication. Cancer cells and the tumor microenvironment release large numbers of exosomes into the blood circulation and have displayed a therapeutic and predictive value in systemic diseases. Integrins expressed on the surface of exosomes drive their selective organotropism and prepare distant sites for metastatic seeding by establishing favorable pre-metastatic niches. Here we show that exosomes from metastasis-bearing lungs or pre-metastatic lungs of mice with melanoma, breast, lung and pancreatic cancer induce TE in mice and express high levels of integrin beta 2 (ITGB2). Instead, exosomes from tumor cell lines, primary tumors or other metastasis-bearing organs did not show any pro-thrombotic properties. Myeloid cells including monocytes/macrophages and neutrophils infiltrating pre- and post-metastatic lungs were the main source of ITGB2+ pro-thrombotic exosomes. Blockade of ITGB2 on lung-derived exosomes, or systemically in mice, prevented exosome-induced platelet aggregation and TE, and reduced metastasis. Examination of the mechanisms of ITGB2-induced TE showed that exosomal ITGB2 interact directly or through fibrin with different binding partners on platelets, and induce their activation and aggregation. Importantly, we found that exosomal ITGB2 levels are elevated in the plasma of PDAC patients prior to TE events in comparison to PDAC patients with no history of TE, and thus might serve as prognostic biomarker of TE. Together, our results provide the first evidence of the establishment of a pro-thrombotic lung niche in different cancer types. Moreover, we identify exosomal ITGB2 as a new target for the prevention and/or treatment of TE, as well as a potential “liquid biopsy” analyte for the early stratification of patients at high risk of TE. Citation Format: Serena Lucotti, Yusuke Ogitani, Candia M. Kenific, Linda Bojmar, Michele Cioffi, Pernille Lauritzen, Henrik Molina, Soren Heissel, Harry B. Lengel, Xiaohong Jing, Haiying Zhang, Irina Matei, Eileen M. O'Reilly, William R. Jarnagin, David R. Jones, James B. Bussel, David Kelsen, Jacqueline F. Bromberg, Diane M. Simeone, David Lyden. The lung pro-thrombotic niche drives cancer-associated thromboembolism via exosomal ITGB2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3138.
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Padoan, Andrea, Mario Plebani, and Daniela Basso. "Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity." International Journal of Molecular Sciences 20, no. 3 (February 5, 2019): 676. http://dx.doi.org/10.3390/ijms20030676.
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Systemic and local chronic inflammation might enhance the risk of pancreatic ductal adenocarcinoma (PDAC), and PDAC-associated inflammatory infiltrate in the tumor microenvironment concurs in enhancing tumor growth and metastasis. Inflammation is closely correlated with immunity, the same immune cell populations contributing to both inflammation and immune response. In the PDAC microenvironment, the inflammatory cell infiltrate is unbalanced towards an immunosuppressive phenotype, with a prevalence of myeloid derived suppressor cells (MDSC), M2 polarized macrophages, and Treg, over M1 macrophages, dendritic cells, and effector CD4+ and CD8+ T lymphocytes. The dynamic and continuously evolving cross-talk between inflammatory and cancer cells might be direct and contact-dependent, but it is mainly mediated by soluble and exosomes-carried cytokines. Among these, tumor necrosis factor alpha (TNFα) plays a relevant role in enhancing cancer risk, cancer growth, and cancer-associated cachexia. In this review, we describe the inflammatory cell types, the cytokines, and the mechanisms underlying PDAC risk, growth, and progression, with particular attention on TNFα, also in the light of the potential risks or benefits associated with anti-TNFα treatments.
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Wu, Guo, Xiaojie Ding, Gang Quan, Jianwei Xiong, Qiang Li, Zhonghu Li, and Yaqin Wang. "Hypoxia-Induced miR-210 Promotes Endothelial Cell Permeability and Angiogenesis via Exosomes in Pancreatic Ductal Adenocarcinoma." Biochemistry Research International 2022 (November 25, 2022): 1–13. http://dx.doi.org/10.1155/2022/7752277.
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Background. Exosomes have been proven to play important diagnostic, regulatory, or communication roles in tumorigenesis, tumor progression, or metastasis; in recent studies, lots of molecules, including miRNAs, were found to be aberrantly expressed in tumor exosomes and were correlated with tumor development. However, studies about the expression, relationship, or control mechanisms of miRNAs in exosomes in pancreatic ductal adenocarcinoma (PDAC) are scarce and urgently needed. The aim of this article was to identify and investigate abnormally expressed miRNAs in PDAC exosomes in vivo and in vitro. Methods. Microarray studies were used to detect aberrantly expressed miRNAs in PDAC exosomes, and miR-210 expression in cells or exosomes was further analyzed by qRT-PCR. Bioinformatics analyses, dual-luciferase assays, WB, and other assays were utilized to explore the miRNA molecular mechanisms. The living cell coculture model and immunofluorescence analysis were employed to image the communication between PDAC cells and endothelial cells. Other biological experiments in the study include a real-time intravital imaging system, EdU, transwell, xenograft models, and so on. Results. miR-210 is significantly expressed in PDAC exosomes and malignant cells. High miR-210 significantly facilitated tumor angiogenesis, cell invasion, and proliferation in PDAC cells. Further mechanistic detection revealed that miR-210 negatively regulated EFNA3 expression and participated in the PI3K/AKT/VEGFA or Wnt/Β-catenin/RHOA pathways, thus promoting tumor angiogenesis and cellular permeability. PDAC cells promote endothelial angiogenesis or permeability via miR-210 transmission by tumor exosomes. Exosomal miR-210 promotes PDAC progression in vivo. Further detection of PDAC plasma exosomal miR-210 suggests that exosomal miR-210 expression was high and significantly associated with vascular invasion and TNM stage and was an independent risk factor for PDAC overall survival. Conclusions. PDAC cell-secreted exosomes could promote angiogenesis and cellular permeability of neighboring endothelial angiogenesis or permeability via miR-210 transmission. Exosomal miR-210 may play important roles in tumor biology and may be a useful prognostic marker in PDAC.
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Li, Zhonghu, Yang Tao, Xiaoya Wang, Peng Jiang, Jie Li, Minjie Peng, Xi Zhang, et al. "Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer." Cellular Physiology and Biochemistry 51, no. 2 (2018): 610–29. http://dx.doi.org/10.1159/000495281.
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Background/Aims: MicroRNAs (miRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal miRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. We aimed to investigate the detailed roles and mechanisms of tumor-generated exosomal miRNAs in progression of PDAC. Methods: miR-222 was identified by miRNA microarray studies in exosomes of PDAC cells, and further analyzed in plasma exosomes of PDAC patients. The regulatory mechanisms of miR-222 were explored by qRT-PCR, WB, dual-luciferase assays and immunofluorescence or confocal analysis. Other biological assays include transwell, xenograft models and so on. Results: miR-222 is significantly high in tumor exosomes or highly invasive PDAC cells. miR-222 could directly regulate p27 to promote cell invasion and proliferation. miR-222 could also activate AKT by inhibiting PPP2R2A expression, thus inducing p27 phosphorylation and cytoplasmic p27 expression to promote cell survival, invasion and metastasis. Expressions of miR-222 and p27 were significantly inversely correlated, and cytoplasmic p27, instead of nuclear p27, was associated with tumor malignancy. miR-222 could be transmitted between PDAC cells via exosome communication, and the exosomal miR-222 communication is functional. Plasma exosomal miR-222 in PDAC patients was high and significantly correlated to tumor size and TNM stage, and was an independent risk factor for PDAC patient survival. Conclusion: Tumor-generated exosomes could promote invasion and proliferation of neighboring tumor cells via miR-222 transmission, the plasma exosomal miR-222 plays important roles and may be a useful prognostic maker in PDAC.
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Batista, Ines, and Sonia Melo. "Exosomes and the Future of Immunotherapy in Pancreatic Cancer." International Journal of Molecular Sciences 20, no. 3 (January 29, 2019): 567. http://dx.doi.org/10.3390/ijms20030567.
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Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, associated with a late diagnosis and a five-year survival rate of 8%. Currently available treatments fall short in improving the survival and quality of life of PDAC patients. The only possible curative option is still the surgical resection of the tumor. Exosomes are extracellular vesicles secreted by cells that transport proteins, lipids, and nucleic acids to other cells, triggering phenotypic changes in the recipient cells. Tumor cells often secrete increased amounts of exosomes. Tumor exosomes are now accepted as important players in the remodeling of PDAC tumor stroma, particularly in the establishment of an immunosuppressive microenvironment. This has sparked the interest in their usefulness as mediators of immunomodulatory effects for the treatment of PDAC. In fact, exosomes are now under study to understand their potential as nanocarriers to stimulate an immune response against cancer. This review highlights the latest findings regarding the function of exosomes in tumor-driven immunomodulation, and the challenges and advantages associated with the use of these vesicles to potentiate immunotherapy in PDAC.
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Chu, Xiangyu, Yinmo Yang, and Xiaodong Tian. "Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs." International Journal of Molecular Sciences 23, no. 17 (August 23, 2022): 9512. http://dx.doi.org/10.3390/ijms23179512.
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment. Tumor cells can secrete exosomes to promote the generation of activated CAFs, meanwhile exosomes secreted by CAFs help promote tumor progression. The aberrant expression of miRNAs in exosomes is involved in the interaction between tumor cells and CAFs, which provides the possibility for the application of exosomal miRNAs in the diagnosis and treatment of PDAC. The current article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and CAFs in the tumor microenvironment, in order to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosome miRNA in human PDAC.
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Richards, Katherine E., Weikun Xiao, and Reginald Hill. "Cancer-Associated Fibroblasts Confer Gemcitabine Resistance to Pancreatic Cancer Cells through PTEN-Targeting miRNAs in Exosomes." Cancers 14, no. 11 (June 6, 2022): 2812. http://dx.doi.org/10.3390/cancers14112812.
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Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer-related death in the United States. Even though the poor prognosis of PDAC is often attributed to late diagnosis, patients with an early diagnosis who undergo tumor resection and adjuvant chemotherapy still show tumor recurrence, highlighting a need to develop therapies which can overcome chemoresistance. Chemoresistance has been linked to the high expression of microRNAs (miRs), such as miR-21, within tumor cells. Tumor cells can collect miRs through the uptake of miR-containing lipid extracellular vesicles called exosomes. These exosomes are secreted in high numbers from cancer-associated fibroblasts (CAFs) within the tumor microenvironment during gemcitabine treatment and can contribute to cell proliferation and chemoresistance. Here, we show a novel mechanism in which CAF-derived exosomes may promote proliferation and chemoresistance, in part, through suppression of the tumor suppressor PTEN. We identified five microRNAs: miR-21, miR-181a, miR-221, miR-222, and miR-92a, that significantly increased in number within the CAF exosomes secreted during gemcitabine treatment which target PTEN. Furthermore, we found that CAF exosomes suppressed PTEN expression in vitro and that treatment with the exosome inhibitor GW4869 blocked PTEN suppression in vivo. Collectively, these findings highlight a mechanism through which the PTEN expression loss, often seen in PDAC, may be attained and lend support to investigations into the use of exosome inhibitors as potential therapeutics to improve the effectiveness of chemotherapy.
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YU, Shaohua, cunren Liu, Jianhua Wang, yuelong Liu, liming Zhang, Yingzi Cong, william Grizzle, and huang-Ge Zhang. "Tumor exosomes inhibit differentiation of bone marrow dendritic cells (49.14)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): S85. http://dx.doi.org/10.4049/jimmunol.178.supp.49.14.
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Abstract The production of exosomes by tumor cells has been implicated in tumor-associated immune suppression. Here we show that, in mice, exosomes produced by TS/A murine mammary tumor cells target CD11b+Gr-1+ myeloid precursors in the bone marrow in vivo and that this is associated with an accumulation of myeloid precursors in the spleen. Moreover, we demonstrate that TS/A exosomes block differentiation of murine myeloid precursor cells into dendritic cells in vitro. Addition of tumor exosomes at day 0 led to a complete block of differentiation into dendritic cells, whereas addition at later time points was less effective. Similarly, exosomes produced by human breast tumor cells inhibited differentiation of human monocytes in vitro. The levels of IL-6 and phosphorylated Stat3 were elevated 12 h after tumor exosome stimulation of murine myeloid precursors, and tumor exosomes were less effective in inhibiting differentiation of bone marrow cells isolated from IL-6 knockout mice. These data suggest that tumor exosome-mediated induction of IL-6 plays a role in blocking bone marrow dendritic cell differentiation.
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Kulkarni, Prateek, Reetobrata Basu, and John J. Kopchick. "Effects of Growth Hormone on Pancreatic Cancer Derived Exosomes." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A1016—A1017. http://dx.doi.org/10.1210/jendso/bvab048.2079.
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Abstract In 2020, the National Cancer Institute (NCI) estimates 57,600 new cases and 47,050 deaths in the US due to pancreatic ductal adenocarcinoma (PDAC). A dismal 10% five-year overall survival rate in PDAC is attributed to late diagnosis, limited treatment options, a remarkably high metastasis rate, and resistance of this cancer to available therapies. Therefore, a better understanding of the mechanisms of how PDAC tumors acquire drug resistance and spread to distal parts of the body are necessary for developing novel therapeutic approaches. Exosomes, microscopic vesicles released from most cells (both tumor and non-tumor) have been recently established to play a significant role in cell to cell communication. Exosomes modulate their target cell responses systematically depending on the nature of exosomal cargoes (nucleic acids, proteins, and lipids). PDAC derived exosomes have been implicated to promote metastasis via forming a pre-metastatic niche of cells as well as enhancing drug resistance. Growth hormone (GH) secreted primarily by the pituitary gland promotes metastasis and drug resistance as shown by plethora of studies. No study has directly assessed the effect of GH on exosomal cargoes in terms of promoting metastases and drug resistance. In this report, we show that GH modulates various pancreatic cancer cell exosomal cargoes which in turn potentially amplifies tumor invasion and metastases. Our data shows that GH treatment on human and mouse PDAC cells increases the exosomal protein levels of TGFβ - a critical inducer of epithelial-to-mesenchymal transition (EMT, a process leading to metastasis). In addition, GH treatment also increases extracellular matrix-degrading enzymes, MMP2 and 9, as well as multi-drug efflux pump ABCC1, ABCB1, and ABCG2 in PDAC cells. These results strongly implicate GH action in driving EMT and chemoresistance via exosomes in pancreatic cancer. Exosomes have a crucial impact especially in the areas of diagnostics and therapeutics. This report is the first to show that GH modulates the effects of exosomes secreted by pancreatic cancer cells. Acknowledgement: This work was supported in part by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by the AMVETS, and Ohio University’s Student Enhancement Award and Edison Biotechnology Institute.
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Hasselluhn, Marie C., Lukas J. Vlahos, Dafydd Thomas, Alvaro Curiel Garcia, Amanda R. Decker, Tanner C. Dalton, Stephen A. Sastra, Carmine F. Palermo, Andrea Califano, and Kenneth P. Olive. "Abstract C032: Combination CAF/myeloid targeting in PDAC." Cancer Research 82, no. 22_Supplement (November 15, 2022): C032. http://dx.doi.org/10.1158/1538-7445.panca22-c032.
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Abstract Immunotherapy has revolutionized clinical care for many cancers, yet these treatments fail to control disease in many patients and new strategies are needed to improve anti-tumor immunity and enhance response rates. There is great need for an increased understanding of the cellular crosstalk within tumors and the identification of stromal and immune populations involved in shaping the tumor microenvironment (TME). Local immunosuppression (LIS) is one of the striking hallmarks of Pancreatic Ductal Adenocarcinoma (PDAC), a disease that is highly resistant to existing immunotherapies. Oncogenic Kras activation in tumor cells promotes the invasion and proliferation of tumor-supporting stromal cells, while excluding cancer-targeted cytotoxic T cells. LIS is mediated by multiple subtypes of cancer-associated fibroblasts (CAFs) and myeloid cells resident within the tumor parenchyma. Multiple prior attempts to reverse LIS in PDAC by targeting individual stromal cell populations have been unsuccessful, alluding to the complexity of stromal crosstalk within the TME. The stromal diversity of PDAC complicates investigating paracrine cascades involving multiple cell types. To decipher diverse drug effects on altering the TME, we employ in vivo studies in mouse models recapitulating the human disease, as well as a novel tumor explant model that enables the short-term culture of intact human or murine PDAC. Importantly, PDAC explants maintain their histopathological architecture and cellular diversity over time. This medium-throughput platform allows for testing of multiple drugs and mechanistic hypotheses in the native PDAC TME. We show in preliminary data that Smoothened inhibition (SMOi) decreases proliferation and activity of myCAFs, but provokes the expansion of CD11b-positive myeloid cells in vivo. Thus, we hypothesize that LIS in PDAC is maintained by a delicate balance between myCAFs and myeloid cells, preventing effective T cell invasion. Single cell RNA-seq data comparing ctrl vs. SMOi-treated murine PDAC elucidates stromal subpopulations involved in the LIS phenotype and guides the identification of myeloid subtypes emerging after SMOi. Strikingly, we demonstrated that simultaneous SMOi and targeting myeloid cells via anti-Gr1 or CCR1 inhibition (CCR1i) significantly elevates cytotoxic T cell numbers within the TME. We are currently investigating whether the activity of these T cells may be further potentiated through combination with immunomodulatory agents. By testing various treatment combination in the same TME, we will identify the best synergistic effects for future immunotherapy approaches in human PDAC. In summary, we are elucidating the complex mechanism behind LIS in PDAC by employing our novel explant culture system alongside in vivo studies. We aim to develop a translatable regimen to neutralize LIS, reactivating the cytotoxic T cells in the tumor periphery to invade, proliferate, and attack cancer cells. Citation Format: Marie C. Hasselluhn, Lukas J. Vlahos, Dafydd Thomas, Alvaro Curiel Garcia, Amanda R. Decker, Tanner C. Dalton, Stephen A. Sastra, Carmine F. Palermo, Andrea Califano, Kenneth P. Olive. Combination CAF/myeloid targeting in PDAC [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C032.
Dissertations / Theses on the topic "Exosomes, myeloid cells, tumor, PDAC"
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Musiu, Chiara. "Role of tumor-derived exosomes on reprogramming myeloid cells." Doctoral thesis, 2021. http://hdl.handle.net/11562/1044432.
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A critical phase of tumor progression is represented by metastases, which are one of the leading causes of cancer-related death. In this process, the intercellular communication plays a fundamental role to promote the formation of a suitable microenvironment for tumor cell implantation and growth in a secondary site, thus leading to the establishment of a pre-metastatic niche (pMN). Interestingly, immune cells, and in particular the myeloid compartment, play a dominant role in the pMN formation. Over the last decades, humanized immune-reconstituted (HIR) mouse models have greatly enhanced the understanding of human cancer biology: the infusion of human hematopoietic stem cells (HSC) in immunodeficient mice allowed to obtain engineered models to study in vivo the interaction between the immune system and human cancer. Exploiting the new technology of single-cell RNA sequencing (sc-RNA seq), we deeply investigated the molecular changes that occur in the immune cells within the lung metastatic site in a pancreatic cancer model. In tumor-bearing mice an enrichment in biological processes of vesicles-mediated transport together with the increased expression of chemotactic factors (S100 proteins) in the monocyte population was unveiled. Indeed, we demonstrated the modulation of human monocytes by soluble factors, i.e. tumor-derived exosomes (TEXs), which resulted in the acquisition of pro-metastatic features, probably induced by molecules transported within TEXs. The inhibition of exosomes secretion with GW4869 administration in tumor-bearing HIR mice did not elicit an impairment in metastases formation. In contrast, by blocking a member of S100 protein family, i.e. S100A9, we were able to dampen the generation of a suitable microenvironment for the pMN formation in tumor-bearing, HIR mice. Finally, we demonstrated the potential role of S100A9 as a cancer biomarker to discriminate the clinical outcome of pancreatic cancer patients, both at molecular and protein level. Collectively, we proved that in the early phases of the pMN formation the immature myeloid compartment exerts a pro-metastatic behaviour in response to TEXs, promoting a more aggressive phenotype with the ability to evade the immunosurveillance and favour the metastatic spread.
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Sartori, Sara. "Tumor-derived exosomes favor immunosuppression and metastatic spread by acting on myeloid cells." Doctoral thesis, 2019. http://hdl.handle.net/11562/994963.
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It is widely recognized that the immune system can be highly affected by tumors through a plethora of mechanisms that allow avoiding an efficient recognition and eradication of cancer cells. Among these mechanisms, tumor secretome, including tumor-derived soluble factors (TDSFs) and, more recently, extracellular vesicles (EVs), is currently drawing much attention in the immune-oncology field. Particularly, by interacting either with stromal or other tumor cells, tumor-derived exosomes (TEX) have been demonstrated as key regulators in cancer development, as well as on the metastatic process. Since myeloid-derived suppressor cells (MDSCs) are critical contributors to the aforementioned processes, we investigated the TEX-MDSCs interaction, highlighting the main functional consequences of this crosstalk. Indeed, we could demonstrate a TEX-mediated effect on MDSC suppressive functions, which was even more striking in the case of bone-marrow naïve monocytes. Furthermore, we demonstrated that this is mainly mediated by iNOS engagement on myeloid cells, possibly induced by molecules enriched within TEX. In addition, the injection of TEX derived from high metastatic cancer cells in naïve tumor-free mice before the tumor challenge with a low metastatic cell line induced an increased spread of cancer cells in the lungs of TEX-treated mice. In the attempt to dampen TEX detrimental effects in tumor models, we blocked exosome secretion through GW4869 drug administration, which did not ameliorate the spread of metastatic cells. On the contrary, by targeting one of the TEX-downstream mediators, i.e. a member of the S100 proteins family, tumor-bearing mice displayed a restrained suppressive tumor network and a strong reduction in the metastatic incidence. Finally, we demonstrated that S100A8/A9 sera levels negatively correlated with distant metastasis-free survival in pancreatic ductal adenocarcinoma (PDAC) patients. In conclusion, our preliminary data highlighted the urgency of developing novel and more effective therapeutic approaches based on a full characterization of TEX-induced pathways in myeloid cells within the local tumor milieu and, moreover, at distal sites of metastasis.
Book chapters on the topic "Exosomes, myeloid cells, tumor, PDAC"
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S. Chauhan, Deepak, Priyanka Mudaliar, Soumya Basu, Jyotirmoi Aich, and Manash K. Paul. "Tumor-Derived Exosome and Immune Modulation." In Extracellular Vesicles - Role in Diseases Pathogenesis and Therapy [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.103718.
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Tumor cells, like most other cells, release exosomes called tumor-derived exosomes (TEX) and are vital for intercellular communication. TEX are membrane-bound extracellular vesicles (EVs), containing unique cargo reminiscent of the parent tumor cells and possess immunomodulatory functions. TEX carries factors that directly promote immunosuppression in the tumor microenvironment and indirectly attract immunosuppressive T-regulatory (Treg) cells. The tumor-secreted exosomes can transfer their cargo by multiple mechanisms like fusion, phagocytosis, and receptor-mediated endocytosis, activating the recipient cells. TEX directly engages and releases cytokines, inactivating natural killer (NK) cells and T-cells and activating apoptosis. Tumor-derived exosomes also release soluble factors to suppress dendritic cell (DC) maturation while activating the expansion of immune-suppressive cells like Myeloid-derived suppressor cells (MDSCs) and Regulatory T (Treg) cells. Several studies have shown the relevance of TEX containing tumor-associated antigens (TAA) in reducing the efficacy of cancer immunotherapy and adoptive cell therapy. Hence understanding the basic biology and mechanism of TEX-mediated immunosuppression is critical in discovering cancer biomarkers and finding better immunotherapy and cell therapy approaches. In this chapter, we have discussed TEX biogenesis, TEX\'s structural and molecular features, TEX-mediated immunosuppression, and its relation to immunotherapy.
Conference papers on the topic "Exosomes, myeloid cells, tumor, PDAC"
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Osipov, Arsen, Jianxin Wang, Shiqi Li, David Choi, Mackenzie Henderson, Jonathan Pachter, Jisook Lee, Dan Maneval, Lei Zheng, and Alex Blair. "Abstract 1588: PEGylated recombinant human hyaluronidase, PEGPH20, significantly enhances the anti-tumor activity of the combination of focal adhesion kinase Inhibitor and anti-PD-1 antibody by targeting CXCR4-expressing myeloid cells in a murine model of PDAC." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-1588.
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