Journal articles: 'Lymph node targeting'

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Hu, Junqing, Jinhao Xu, Mingyue Li, Yanping Zhang, Huaiqiang Yi, Jiangning Chen, Lei Dong, Junfeng Zhang, and Zhen Huang. "Targeting Lymph Node Sinus Macrophages to Inhibit Lymph Node Metastasis." Molecular Therapy - Nucleic Acids 16 (June 2019): 650–62. http://dx.doi.org/10.1016/j.omtn.2019.04.016.

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Kim, Jihoon, Paul A. Archer, and Susan N. Thomas. "Innovations in lymph node targeting nanocarriers." Seminars in Immunology 56 (August 2021): 101534. http://dx.doi.org/10.1016/j.smim.2021.101534.

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Wang, Qiu, Zhe Wang, Xinxin Sun, Qikun Jiang, Bingjun Sun, Zhonggui He, Shenwu Zhang, Cong Luo, and Jin Sun. "Lymph node-targeting nanovaccines for cancer immunotherapy." Journal of Controlled Release 351 (November 2022): 102–22. http://dx.doi.org/10.1016/j.jconrel.2022.09.015.

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Pfister, David, Matthias Schmidt, Friederike Haidl, Daniel Porres-Knoblauch, Alexander Drzezga, and Axel Heidenreich. "Is there an additional benefit of Tc-99m-PSMA-guided gamma probe use for salvage lymph node dissection in recurrent prostate cancer." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): e591-e591. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.e591.

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e591 Background: PSMA-PET/CT is the most sensitive diagnostic tool in biochemical recurrent prostate cancer to detect minimal metastatic disease. However, it may be difficult to localize small PSMA-positive lymph nodes intraoperatively. Therefore, it was the aim to investigate whether preoperative Tc-99m-PSMA targeting may improve intraoperative tumor localization by use of a gamma probe. Methods: In 13 Patients Ga-68-PSMA-PET/CT identified iliac lymph nodes in patients suitable for salvage lymph node dissection. On the day before operation a mean activity of 480 MBq Tc-99m-PSMA was injected and gamma camera scintigraphy + SPECT was performed 4-5 hours after tracer application. About 24 hours after tracer application a salvage lymph node dissection was performed on the side of initial suspicious lymph node metastases. Sensitivity, specifity, pos and neg. predictive values were calulated for PSMA-PET/CT and gamma probe use to analyse the additional use. Results: In 9 / 13 patients PSMA-positive metastatic lymph nodes were identified in Ga-68 PSMA-PET/CT. A total of 156 lymph nodes were removed with 14 lymph nodes in 9 patients being positive in histopathologic examination. Sensitivity, specifity, pos and neg. predictive values for PSMA PET/CT and gamma probe were 85% and 79%, 99% and 100%, 85% and 100% and 99% and 98% respectively. In one patient only gamma probe use identified a pathologic lymph node. Conclusions: Gamma probe guided salvage lymph node dissection in PSA recurrent prostate cancer is feasible and had a high concordance with PSMA-PET/CT. However, the additional diagnostic benefit is limited compared to PSMA-PET/CT because in only one patient (7%) a positive lymph node could be identified with the use of the gamma probe outside the standard operative area in salvage lymph node dissection.

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Jiang, Hao, Qin Wang, and Xun Sun. "Lymph node targeting strategies to improve vaccination efficacy." Journal of Controlled Release 267 (December 2017): 47–56. http://dx.doi.org/10.1016/j.jconrel.2017.08.009.

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Sun, In-Cheol, SeongHoon Jo, Diego Dumani, Wan Su Yun, Hong Yeol Yoon, Dong-Kwon Lim, Cheol-Hee Ahn, Stanislav Emelianov, and Kwangmeyung Kim. "Theragnostic Glycol Chitosan-Conjugated Gold Nanoparticles for Photoacoustic Imaging of Regional Lymph Nodes and Delivering Tumor Antigen to Lymph Nodes." Nanomaterials 11, no. 7 (June 28, 2021): 1700. http://dx.doi.org/10.3390/nano11071700.

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Lymph node mapping is important in cancer immunotherapy because the morphology of lymph nodes is one of the crucial evaluation criteria of immune responses. We developed new theragnostic glycol-chitosan-coated gold nanoparticles (GC-AuNPs), which highlighted lymph nodes in ultrasound-guided photoacoustic (US/PA) imaging. Moreover, the ovalbumin epitope was conjugated GC-AuNPs (OVA-GC-AuNPs) for delivering tumor antigen to lymph node resident macrophage. In vitro studies proved the vigorous endocytosis activity of J774A.1 macrophage and consequent strong photoacoustic signals from them. The macrophages also presented a tumor antigen when OVA-GC-AuNPs were used for cellular uptake. After the lingual injection of GC-AuNPs into healthy mice, cervical lymph nodes were visible in a US/PA imaging system with high contrast. Three-dimensional analysis of lymph nodes revealed that the accumulation of GC-AuNPs in the lymph node increased as the post-injection time passed. Histological analysis showed GC-AuNPs or OVA-GC-AuNPs located in subcapsular and medullar sinuses where macrophages are abundant. Our new theragnostic GC-AuNPs present a superior performance in US/PA imaging of lymph nodes without targeting moieties or complex surface modification. Simultaneously, GC-AuNPs were able to deliver tumor antigens to cause macrophages to present the OVA epitope at targeted lymph nodes, which would be valuable for cancer immunotherapy.

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MacDonald, Gene H., and Robert E. Johnston. "Role of Dendritic Cell Targeting in Venezuelan Equine Encephalitis Virus Pathogenesis." Journal of Virology 74, no. 2 (January 15, 2000): 914–22. http://dx.doi.org/10.1128/jvi.74.2.914-922.2000.

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ABSTRACT The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which migrate to the draining lymph node following activation. A point mutation in the E2 glycoprotein gene of VEE that renders the virus avirulent and compromises its ability to spread beyond the draining lymph blocked the appearance of virally infected dendritic cells in the lymph node in vivo. A second-site suppressor mutation that restores viral spread to lymphoid tissues and partially restore virulence likewise restored the ability of VEE to infect dendritic cells in vivo.

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Xi, Xiaobo, Lijun Zhang, Guihong Lu, Xiaoyong Gao, Wei Wei, and Guanghui Ma. "Lymph Node-Targeting Nanovaccine through Antigen-CpG Self-Assembly Potentiates Cytotoxic T Cell Activation." Journal of Immunology Research 2018 (June 19, 2018): 1–10. http://dx.doi.org/10.1155/2018/3714960.

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Therapeutic vaccines that arouse the cytotoxic T cell immune response to reject infected cells have been investigated extensively for treating disease. Due to the large amounts of resident antigen-presenting cells (APCs) and T cells in lymph nodes, great efforts have been made to explore the strategy of targeting lymph nodes directly with nanovaccines to activate T cells. However, these nanovaccines still have several problems, such as a low loading efficiency and compromised activity of antigens and adjuvants derived from traditional complicated preparation. There are also safety concerns about materials synthesized without FDA approval. Herein, we construct an assembled nanoparticle composed of an antigen (ovalbumin, OVA) and adjuvant (CpG) to ensure its safety and high loading efficiency. The activity of both components was well preserved due to the mild self-assembly process. The small size, narrow distribution, negative charge, and good stability of the nanoparticle endow these nanovaccines with superior capacity for lymph node targeting. Correspondingly, the accumulation at lymph nodes can be improved by 10-fold. Subsequently, due to the sufficient APC internalization and maturation in lymph nodes, ~60% of T cells are stimulated to proliferate and over 70% of target cells are specifically killed. Based on the effective and quick cellular immune response, the assembled nanoparticles exhibit great potential as therapeutic vaccines.

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Chu, Maoquan, Shu Zhuo, Jiang Xu, Qiunan Sheng, Shengke Hou, and Ruifei Wang. "Liposome-coated quantum dots targeting the sentinel lymph node." Journal of Nanoparticle Research 12, no. 1 (February 15, 2009): 187–97. http://dx.doi.org/10.1007/s11051-009-9593-2.

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Grote, Thomas, Amy H. Hughes, Cathy C. Rimmer, Dale A. Less, and Amy P. Abernethy. "Targeting Lymph Node Retrieval and Assessment in Stage II Colon Cancer: A Quality Outcome Community-Based Cancer Center Study." Journal of Oncology Practice 4, no. 2 (March 2008): 55–58. http://dx.doi.org/10.1200/jop.0822001.

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Purpose Adequate lymph node evaluation is required for the proper staging of colon cancer. The current recommended number of lymph nodes that should be retrieved and assessed is 12. Methods The multidisciplinary Gastrointestinal Tumor Board at the Derrick L. Davis Forsyth Regional Cancer Center reviewed and recommended that a minimum of 12 lymph nodes be examined in all cases of colon cancer to ensure proper staging. This recommendation occurred at the end of the first quarter of 2005. To ensure this new standard was being followed, an outcomes study looking at the number of lymph nodes evaluated in stage II colon cancer was initiated. All patients with stage II colon cancer diagnosed between 2004 and 2006 were reviewed. Results There was a statistically significant improvement in the number of stage II colon cancer patients with 12 or more lymph nodes evaluated. Before the Gastrointestinal Tumor Board's recommendation, 49% (40 out of 82 patients) had 12 or more lymph nodes sampled. The median number of lymph nodes evaluated was 11. After the Gastrointestinal Tumor Board's recommendation, 79% (70 out of 88 patients) had 12 or more lymph nodes sampled. The median number of lymph nodes was 16. Conclusion Multidisciplinary tumor boards can impact the quality of care of patients as demonstrated in this study. Although we do not yet have survival data on these patients, based on the previous literature referenced in this article, we would expect to see an improvement in survival rates in patients with 12 or more nodes retrieved and assessed.

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Becker, Y. "Transfer of antivirals to skin Langerhans cells--a novel approach to anti-HIV treatment by "antiviral peplotion"." Acta Biochimica Polonica 43, no. 1 (March 31, 1996): 175–81. http://dx.doi.org/10.18388/abp.1996_4575.

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The analysis of the history of the research on antivirals especially the treatment of HIV-1 infected individuals with antivirals which were developed prior to the current AIDS epidemic led to suggest a different approach to the targeting of antivirals in the AIDS patients. Since HIV-1 replication in infected individuals occurs in the lymph nodes, it is suggested that modified anti-HIV-1 drugs should be applied to Langerhans cells in the skin. The Langerhans cells can serve as the carries of the antiviral drugs attached to their surfaces due to their ability to migrate from the skin through the lymph vessels and to home to the lymph node. At that site Langerhans cells interact with T cells. Transfer of the anti-HIV-1 drugs to infected CD4+ T cells in the lymph node will reduce virus replication in the lymph nodes and will reduce the cytotoxic systemic effects of the antiviral drug. Such an antiviral treatment requires the development of efficient methods of drug delivery through the skin.

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Kojima, Toru, Yuichi Watanabe, Yuuri Hashimoto, Shinji Kuroda, Yasumoto Yamasaki, Shuya Yano, Hiroshi Tazawa, et al. "Telomerase-specific virotherapy targeting lymph node micrometastasis of human cancer." Okayama Igakkai Zasshi (Journal of Okayama Medical Association) 125, no. 1 (2013): 9–12. http://dx.doi.org/10.4044/joma.125.9.

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Liu, Haipeng, Kelly D. Moynihan, Yiran Zheng, Gregory L. Szeto, Adrienne V. Li, Bonnie Huang, Debra S. Van Egeren, Clara Park, and Darrell J. Irvine. "Structure-based programming of lymph-node targeting in molecular vaccines." Nature 507, no. 7493 (February 16, 2014): 519–22. http://dx.doi.org/10.1038/nature12978.

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Selim, A., M. El-Haig, and W. Gaede. "Duplex real-time PCR assay targeting insertion elements IS1081 and IS6110 for detection of Mycobacterium bovis in lymph nodes of cattle." Biotehnologija u stocarstvu 30, no. 1 (2014): 45–59. http://dx.doi.org/10.2298/bah1401045s.

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The development of a reliable and rapid screening test for detection of Mycobacterium bovis (M. bovis) helps in control of bovine tuberculosis. The aim of this study was evaluate a sensitive and specific assay for detecting M. bovis DNA in lymph nodes with lesions suggestive to tuberculosis taken from slaughtered cattle. A duplex real-time PCR assay was developed for the identification of M. bovis targeting insertion elements (IS) IS1081 and IS6110 in one internally controlled reaction. M. bovis DNA extraction protocols from tissue samples were evaluated. The specificity and sensitivity of the assay were evaluated for detecting serial dilutions of reference Mycobacteria strains as well as from spiked lymph node homogenate. Results revealed that microscopical examination of 600 lymph nodes with tuberculous-like lesion for detection of Acid-fast bacilli (AFB) showed a detection rate of 96.6%, compared to 98% M. bovis with duplex real-time PCR. The reproducible detection limit of the IS1081-PCR was 10 M. bovis cells/ml and the IS6110-PCR was 100 M. bovis cells/ml. Besides, both primer set of PCR protocol could detect 20 M. bovis cells/ml in spiked lymph node tissue. The assay was evaluated on 19 bacterial strains and was determined to be 100% specific for M. bovis. We suggest that the IS1081-PCR is a good candidate assay for routine screening of cattle lymph nodes and other tissue for M. bovis infection.

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Zhang, Lingyun, Xin Zhan, Dingding Yan, and Zhihua Wang. "Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1." International Journal of Gynecologic Cancer 26, no. 5 (June 2016): 810–16. http://dx.doi.org/10.1097/igc.0000000000000694.

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ObjectiveThe aims of this study were to discover if increased circulating microRNA-21 (miR-21) expression in serum is associated with lymph node metastasis in patients with cervical cancer and look further into the molecular mechanism of these. Whole-blood samples from 89 patients who have been histopathologically confirmed as having cervical cancer and 20 control subjects were collected, and then the association between lymph node metastasis and the level of circulating miR-21 was compared. Then cervical cancer cell lines HeLa (HPV-18 DNA+, E6/E7RNA+) and HT-3 (HPV DNA−, E6/E7RNA−) were used to confirm the interaction between miR-21 and RASA1. The role of RASA1 in cervical cancer cell migration was also studied in HeLa. Increased circulating miR-21 expression in serum is associated with lymph node metastasis in patients with cervical cancer. MicroRNA-21 reduces RASA1 expression in cervical cancer cell lines and promotes cervical cancer cell migration via RASA1. Furthermore, Ras-induced epithelial-mesenchymal transition contributes to miR-21/RASA1 axis promoting cervical cancer cell migration. Circulating miR-21 in serum could be a promising biomarker in auxiliary diagnosis of lymph node metastasis in cervical cancer, and inhibition of miR-21/RASA1 axis could be a possible strategy to restrain migration of cervical cancer.

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Rovera, Christopher, Ilona Berestjuk, Margaux Lecacheur, Cassandre Tavernier, Serena Diazzi, Sabrina Pisano, Marie Irondelle, et al. "Secretion of IL1 by Dedifferentiated Melanoma Cells Inhibits JAK1-STAT3–Driven Actomyosin Contractility of Lymph Node Fibroblastic Reticular Cells." Cancer Research 82, no. 9 (February 22, 2022): 1774–88. http://dx.doi.org/10.1158/0008-5472.can-21-0501.

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Abstract Fibroblastic reticular cells (FRC) are immunologically specialized myofibroblasts that control the elasticity of the lymph node, in part through their contractile properties. Swelling of tumor-draining lymph nodes is a hallmark of lymphophilic cancers such as cutaneous melanoma. Melanoma displays high intratumoral heterogeneity with the coexistence of melanoma cells with variable differentiation phenotypes from melanocytic to dedifferentiated states. Factors secreted by melanoma cells promote premetastatic lymph node reprograming and tumor spreading. Elucidating the impact of the melanoma secretome on FRC could help identify approaches to prevent metastasis. Here we show that melanocytic and dedifferentiated melanoma cells differentially impact the FRC contractile phenotype. Factors secreted by dedifferentiated cells, but not by melanocytic cells, strongly inhibited actomyosin-dependent contractile forces of FRC by decreasing the activity of the RHOA–RHO–kinase (ROCK) pathway and the mechano-responsive transcriptional coactivator Yes1 associated transcriptional regulator (YAP). Transcriptional profiling and biochemical analyses indicated that actomyosin cytoskeleton relaxation in FRC is driven by inhibition of the JAK1-STAT3 pathway. This FRC relaxation was associated with increased FRC proliferation and activation and with elevated tumor invasion in vitro. The secretome of dedifferentiated melanoma cells also modulated the biomechanical properties of distant lymph node in premetastatic mouse models. Finally, IL1 produced by dedifferentiated cells was involved in the inhibition of FRC contractility. These data highlight the role of the JAK1-STAT3 and YAP pathways in spontaneous contractility of resting FRC. They also suggest that dedifferentiated melanoma cells specifically target FRC biomechanical properties to favor tumor spreading in the premetastatic lymph node niche. Targeting this remote communication could be an effective strategy to prevent metastatic spread of the disease. Significance: Communication between dedifferentiated melanoma cells and lymph node fibroblasts reprograms the biomechanical properties of the premetastatic lymph node niche to promote tumor invasion. See related commentary by Lund, p. 1692

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Qiu, Shanshan, Jianfeng Zeng, Yi Hou, Lei Chen, Jianxian Ge, Ling Wen, Chunyan Liu, Youjiu Zhang, Ran Zhu, and Mingyuan Gao. "Detection of lymph node metastasis with near-infrared upconversion luminescent nanoprobes." Nanoscale 10, no. 46 (2018): 21772–81. http://dx.doi.org/10.1039/c8nr05811c.

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Takeuchi, Hiroya, Hirofumi Kawakubo, Yoshiro Saikawa, Tadaki Nakahara, Tai Omori, Makio Mukai, and Yuko Kitagawa. "Sentinel lymph node mapping for T1 esophageal cancer." Journal of Clinical Oncology 30, no. 4_suppl (February 1, 2012): 7. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.7.

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7 Background: Extended radical esophagectomy with three-field lymph node dissection has been recognized as the standard procedure for thoracic esophageal cancer in Japan, even for clinically T1N0 cases. However, to eliminate the uniform application of the highly invasive surgery, we hypothesized that sentinel lymph node (SLN) mapping would play a key role to obtain individual information and allows modification of the surgical procedure for early esophageal cancer. Methods: We have established radio-guided method to detect SLNs in patient with early esophageal cancer using endoscopic injection of technetium-99m tin colloid. Preoperative lymphoscintigraphy and intra-operative use of hand held gamma probe were reliable to locate the radioactive SLNs. Intra-operative gamma probing was also feasible in thoracoscopic or laparoscopic surgery using a special gamma detector which is introducible from trocar ports. Results: SLN mapping has been performed for 70 patients with clinically N0 and early (pT1) esophageal cancer in our institute since 1999. Detection rate of hot node using our procedure was 94% (66/70). The mean number of sentinel nodes per case was 4.6. Twenty-one of 23 cases (91%) with lymph node metastasis showed positive SLNs. Accuracy of metastatic status based on SLN was 97% (64/66). SLNs widely spread from cervical to abdominal areas. In more than 80% of the cases, at least one SLN was located in the 2nd or 3rd compartment of regional lymph nodes. However, 56 (85%) of 66 patients had no lymph node metastasis or metastasis (+) only in SLNs. Conclusions: Our results suggest that SLN concept for clinically N0 and T1 esophageal cancer could be validated. Theoretically more than 80% of patients with pT1b esophageal cancer may be controlled by local treatments such as surgery and chemoradiotherapy targeting primary tumors plus their SLNs. Individualized selective and modified lymphadenectomy targeted on SLN basins for clinically N0 early esophageal cancer should become feasible and clinically useful as less invasive surgical procedures.

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An, Myunggi, Meng Li, Jingchao Xi, and Haipeng Liu. "Silica Nanoparticle as a Lymph Node Targeting Platform for Vaccine Delivery." ACS Applied Materials & Interfaces 9, no. 28 (July 3, 2017): 23466–75. http://dx.doi.org/10.1021/acsami.7b06024.

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Lian, Jeffrey, Aleksandra J. Ozga, Caroline L. Sokol, and Andrew D. Luster. "Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization." Cell Reports 31, no. 8 (May 2020): 107679. http://dx.doi.org/10.1016/j.celrep.2020.107679.

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Suzuki, Takayoshi, Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Daisuke Yoshida, et al. "Effectiveness of superselective intra-arterial chemoradiotherapy targeting retropharyngeal lymph node metastasis." European Archives of Oto-Rhino-Laryngology 273, no. 10 (February 13, 2016): 3331–36. http://dx.doi.org/10.1007/s00405-016-3933-5.

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Roukos, Dimitrios H., and Angelos M. Kappas. "Targeting the optimal extent of lymph node dissection for gastric cancer." Journal of Surgical Oncology 81, no. 2 (September 26, 2002): 59–62. http://dx.doi.org/10.1002/jso.10153.

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Becker, William J., Prakash Nagarkatti, and Mitzi Nagarkatti. "Allograft transplantation provokes miRNA 297–669 cluster that reduces T regulatory cell generation through targeting TGF-β2." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 55.32. http://dx.doi.org/10.4049/jimmunol.200.supp.55.32.

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Abstract T regulatory cells (Tregs) are anti-inflammatory cells capable of quelling the harshest immune responses. Accordingly, Treg therapy is rapidly becoming a viable treatment option for patients stricken with autoimmune diseases or those in need of an organ transplant. In a model of allotransplantation, via microarray, our work identified miRNA cluster 297–669 is induced in CD4+ cells in the lymph nodes draining the allograft in C57BL/6 mice given a C3H skin transplant. One member of this cluster, miR 466a-3p, is induced in a co-culture of lymph node cells stimulated with alloantigen in vitro. We have shown that this miRNA specifically targets transforming growth factor beta 2 (TGF-β2). The reduction in TGF-β2 levels in draining lymph node CD4+ T cells caused a resultant decrease in the generation of FoxP3+ Tregs, both within the graft and in the draining lymph node. Furthermore, blocking the effect of this miRNA using a specific locked nucleic acid (LNA) reversed this effect. Generation of Tregs using transforming growth factor beta1 (TGF-β1), interleukin-2 and CD3/CD28 is the most common method of induction. Here we show that replacing TGF-β1 with TGF-β2 has no detrimental effect on Treg induction. Indeed, Tregs induced with TGF-β2 have equal in vivo suppressive capability as TGF-β1 Tregs in a skin graft model when adoptively transferred. Moreover, these TGF-β2 Tregs have increased inducible T-cell costimulatory (ICOS) expression. The ability of TGF-β2 to induce Tregs was reversed when a TGF-β2 neutralizing antibody was used, while this antibody had no effect on TGF-β1 induced Tregs. The work herein describes, for the first time, a novel isoform of TGF-β that may be involved in the generation of Tregs with implications in all areas of immunology.

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Jirátová, Markéta, Andrea Gálisová, Maria Rabyk, Eva Sticová, Martin Hrubý, and Daniel Jirák. "Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors." Molecules 26, no. 1 (December 31, 2020): 146. http://dx.doi.org/10.3390/molecules26010146.

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Early detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an in vivo animal tumor model. Our approach is based on mannan-based copolymers synergistically targeting: (1) SLNs and macrophage-infiltrated solid tumor areas via the high-affinity DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) receptors and (2) tumors via the enhanced permeability and retention (EPR) effect. The polymer conjugates were modified with the imaging probes for visualization with magnetic resonance (MR) and fluorescence imaging, respectively, and with poly(2-methyl-2-oxazoline) (POX) to lower unwanted accumulation in internal organs and to slow down the biodegradation rate. We demonstrated that these polymer conjugates were successfully accumulated in tumors, SLNs and other lymph nodes. Modification with POX resulted in lower accumulation not only in internal organs, but also in lymph nodes and tumors. Importantly, we have shown that mannan-based polymer carriers are non-toxic and, when applied to an in vivo murine cancer model, and offer promising potential as the versatile imaging agents.

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Zukancic, Danijela, Estelle J. A. Suys, Emily H. Pilkington, Azizah Algarni, Hareth Al-Wassiti, and Nghia P. Truong. "The Importance of Poly(ethylene glycol) and Lipid Structure in Targeted Gene Delivery to Lymph Nodes by Lipid Nanoparticles." Pharmaceutics 12, no. 11 (November 9, 2020): 1068. http://dx.doi.org/10.3390/pharmaceutics12111068.

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Targeted delivery of nucleic acids to lymph nodes is critical for the development of effective vaccines and immunotherapies. However, it remains challenging to achieve selective lymph node delivery. Current gene delivery systems target mainly to the liver and typically exhibit off-target transfection at various tissues. Here we report novel lipid nanoparticles (LNPs) that can deliver plasmid DNA (pDNA) to a draining lymph node, thereby significantly enhancing transfection at this target organ, and substantially reducing gene expression at the intramuscular injection site (muscle). In particular, we discovered that LNPs stabilized by 3% Tween 20, a surfactant with a branched poly(ethylene glycol) (PEG) chain linking to a short lipid tail, achieved highly specific transfection at the lymph node. This was in contrast to conventional LNPs stabilized with a linear PEG chain and two saturated lipid tails (PEG-DSPE) that predominately transfected at the injection site (muscle). Interestingly, replacing Tween 20 with Tween 80, which has a longer unsaturated lipid tail, led to a much lower transfection efficiency. Our work demonstrates the importance of PEGylation in selective organ targeting of nanoparticles, provides new insights into the structure–property relationship of LNPs, and offers a novel, simple, and practical PEGylation technology to prepare the next generation of safe and effective vaccines against viruses or tumours.

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Crecente-Campo, José, Tommaso Virgilio, Diego Morone, Cristina Calviño-Sampedro, Iago Fernández-Mariño, Ana Olivera, Rubén Varela-Calvino, Santiago F. González, and María J. Alonso. "Design of polymeric nanocapsules to improve their lympho-targeting capacity." Nanomedicine 14, no. 23 (December 2019): 3013–33. http://dx.doi.org/10.2217/nnm-2019-0206.

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Aim: To design lympho-targeted nanocarriers with the capacity to enhance the activity of associated drugs/antigens whose target is within the lymphatic system. Materials & methods: Inulin (INU)-based nanocapsules (NCs), negatively charged and positively charged chitosan NCs were prepared by the solvent displacement techniques. The NCs were produced in two sizes: small (70 nm) and medium (170–250 nm). Results: In vitro results indicated that small NCs interacted more efficiently with dendritic cells than the larger ones. The study of the NCs biodistribution in mice, using 3D reconstruction of the popliteal lymph node, showed that small INU NCs have the greatest access and uniform accumulation in different subsets of resident immune cells. Conclusion: Small and negatively charged INU NCs have a potential as lympho-targeted antigen/drug nanocarriers.

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Wang, Sa, Linda M. Ernst, Brian R. Smith, Giovanni Tallini, John G. Howe, Jill Crouch, and Dennis L. Cooper. "Systemic Tropheryma whippleii Infection Associated With Monoclonal B-Cell Proliferation: A Helicobacter pylori–Type Pathogenesis?" Archives of Pathology & Laboratory Medicine 127, no. 12 (December 1, 2003): 1619–22. http://dx.doi.org/10.5858/2003-127-1619-stwiaw.

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Abstract We report a case of Whipple disease in a 55-year-old woman who presented with arthralgia, weight loss, and lymphadenopathy. Tropheryma whippleii bacilli were identified in the mesenteric lymph nodes by diastase-resistant periodic acid–Schiff stain and confirmed by electron microscopy. Retrospectively, previous biopsy specimens from the duodenum and right axillary lymph node of this patient, which were initially considered to demonstrate reactive changes, also showed features consistent with involvement by Whipple disease. At the time of presentation, a large κ-restricted monoclonal B-cell population with the phenotype CD20+CD19+CD5−CD10− was identified in the patient's peripheral blood, lymph nodes, and bone marrow by flow cytometry study. The monoclonality of the mesenteric lymph node B cells was confirmed by immunohistochemical stain for κ chain after antigen retrieval and also by polymerase chain reaction with the primer set targeting FR2-VH. Routine cytogenetic study failed to reveal any chromosomal abnormalities, and polymerase chain reaction for Bcl-2 major and minor breakpoint cluster of t(14:18) was not detected. The monoclonal B cells have persisted in blood for the entire follow-up period (10 months). The possibility of reactive monoclonal B-cell proliferation versus Whipple disease–related B-cell lymphoma is discussed.

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De Gouw, Didi, Bastiaan Klarenbeek, Mark Rijpkema, Kiek Verrijp, Maroeska Rovers, Camiel Rosman, and Chella Van Der Post. "RA07.02: IDENTIFYING TUMOR MARKERS IN ESOPHAGEAL ADENOCARCINOMA AND LYMPH NODE METASTASES FOR TARGETED FLUORESCENCE IMAGING." Diseases of the Esophagus 31, Supplement_1 (September 1, 2018): 34. http://dx.doi.org/10.1093/dote/doy089.ra07.02.

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Abstract Background Neoadjuvant chemoradiotherapy (nCRT) followed by resection of the tumor with two field lymphadenectomy is a standard treatment for esophageal cancer. After nCRT, however, in more than 70% of patients no lymph node metastases are found, suggesting extensive overtreatment. Tumor-targeted fluorescence imaging is a promising technique to detect lymph node metastases intra-operatively and guide personalized resection. The aim of this study is to identify potential viable tumor markers for fluorescence imaging of lymph node metastases in patients with esophageal adenocarcinoma (EAC). Methods Immunohistochemistry (IHC) was performed on tissue microarrays from EAC’s patients that underwent surgical resection between 2007 and 2016. Patients were subdivided in five groups, non-pretreated patients with and without metastatic lymph nodes, complete responders, partial responders and non-responders after nCRT. Five membranous markers, c-MET, CAIX, EGFR, EpCAM, HER2, and two cytoplasmic markers, VEGF-A and VEGF-A receptor were included. Tumor marker expression was scored on intensity (none (0), slight (1), moderate (2), strong (3)) and the percentage of positive cells (estimation). Threshold for positive detection rate was defined as an intensity of ≥ 2 in more than 10% the cells. Results EpCAM showed the highest expression in metastastic lymph nodes, with a median intensity of 3 (range 2–3) in > 70% of the tumor cells. Expression was found in 37 out of 39 EAC’s (95%). VEGF-A and CAIX expression was observed in 28 of 33 (85%) and 10 of 33 (30%) of metastatic lymph nodes and 34 of 39 (87%) and 17 of 39 (44%) in the primary EAC’s, respectively. For the other tumor biomarkers the detection rate ranged between 0 and 11% for metastatic lymph nodes and primary EAC’s. Only EpCAM and VEGF-A showed weak, non-specific staining in the fibrotic tissue. Conclusion High expression rates in primary EAC and metastatic lymph nodes were observed using immunohistochemical antibodies for EpCAM, VEGF-A and CA-IX, making these clinically relevant viable EAC tumor markers. A phase 1 dose finding study targeting VEGF-A by Bevacizumab-800-CW in patient with EAC is in preparation. Disclosure All authors have declared no conflicts of interest.

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Zhang, Weidong, Myunggi An, Jingchao Xi, and Haipeng Liu. "Targeting CpG Adjuvant to Lymph Node via Dextran Conjugate Enhances Antitumor Immunotherapy." Bioconjugate Chemistry 28, no. 7 (July 6, 2017): 1993–2000. http://dx.doi.org/10.1021/acs.bioconjchem.7b00313.

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Nakamura, Takashi, and Hideyoshi Harashima. "Dawn of lipid nanoparticles in lymph node targeting: Potential in cancer immunotherapy." Advanced Drug Delivery Reviews 167 (December 2020): 78–88. http://dx.doi.org/10.1016/j.addr.2020.06.003.

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Ludewig, Burkhard, Qian Chai, Lucas Onder, Elke Scandella, Tim Sparwasser, Sanjiv Luther, Volker Thiel, Thomas Rülicke, and Thomas Hehlgans. "CCL19-Cre transgenics: targeting lymph node fibroblastic reticular cells in vivo (44.14)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 44.14. http://dx.doi.org/10.4049/jimmunol.188.supp.44.14.

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Abstract The paracortex of lymph nodes (LNs) harbors a sponge-like scaffold of stromal cells known as fibroblastic reticular cells (FRCs). A major function of FRCs is to build and enwrap the conduit system of collagen fibers that directs interstitial fluids from the afferent lymph through the T-cell zone to HEVs. Furthermore, FRCs regulate T-cell migration and survival by producing the chemokines CCL19 and CCL21. To gain further knowledge on the biology of FRCs and possibly other stromal cell subsets, we have generated a bacterial artificial chromosome (BAC)-transgenic mouse model that utilizes the CCL19 promoter to direct the Cre-recombinase to LN stromal cells. Crossing of CCL19-Cre mice to the R26-EYFP reporter revealed that transgene expression in LNs was almost exclusively confined to podoplanin+CD31- cells. Likewise, transgene activity in spleens and Peyer’s patches of CCL19-Cre mice was largely restricted to FRC-like cells, i.e. stromal cells within the T cell zone and the T-B border. Selective ablation of the lymphotoxin-beta receptor on CCL19-Cre-positive cells resulted in profound changes in the development and organization of secondary lymphoid organs. Taken together, stromal CCL19-Cre expression is well-suited (i) to characterize the development of LN FRCs in vivo, (ii) to molecularly dissect the contribution of stromal cells to lymphoid organogenesis, and (iii) to address the function of LN FRCs in the generation of innate and adaptive immune responses.

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Smit, Laura A., Delfine Y. H. Hallaert, René Spijker, Bart de Goeij, Annelieke Jaspers, Arnon P. Kater, Marinus H. J. van Oers, Carel J. M. van Noesel, and Eric Eldering. "Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity." Blood 109, no. 4 (October 12, 2006): 1660–68. http://dx.doi.org/10.1182/blood-2006-05-021683.

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Abstract The gradual accumulation of chronic lymphocytic leukemia (B-CLL) cells is presumed to derive from proliferation centers in lymph nodes and bone marrow. To what extent these cells possess the purported antiapoptotic phenotype of peripheral B-CLL cells is unknown. Recently, we have described that, in B-CLL samples from peripheral blood, aberrant apoptosis gene expression was not limited to protective changes but also included increased levels of proapoptotic BH3-only member Noxa. Here, we compare apoptosis gene profiles from peripheral blood B-CLL (n = 15) with lymph node B-CLL (> 90% CD5+/CD19+/CD23+ lymphocytes with Ki67+ centers; n = 9). Apart from expected differences in Survivin and Bcl-xL, a prominent distinction with peripheral B-CLL cells was the decreased averaged level of Noxa in lymph nodes. Mcl-1 protein expression showed a reverse trend. Noxa expression could be reduced also in vitro by CD40 stimulation of peripheral blood B-CLL. Direct manipulation of Noxa protein levels was achieved by proteasome inhibition in B-CLL and via RNAi in model cell lines. In each instance, cell viability was directly linked with Noxa levels. These data indicate that suppression of Noxa in the lymph node environment contributes to the persistence of B-CLL at these sites and suggest that therapeutic targeting of Noxa might be beneficial.

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Erik, Slinger, Arnon P. Kater, Rachel Thijssen, and Eric Eldering. "Targeting BCR-Independent Proliferation of CLL Cells." Blood 126, no. 23 (December 3, 2015): 2916. http://dx.doi.org/10.1182/blood.v126.23.2916.2916.

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Abstract The clinical success of PI3K and Btk inhibitors that block upstream BCR signals, has been primarily attributed to inhibition of adhesion and migration of CLL cells. However, the effects of these inhibitors on the proliferative capacity of CLL cells is largely unknown. Interestingly, in vitro BCR triggering does not induce proliferation of CLL cells. Instead, we have found that activated T cell-derived signals, specifically CD40L and IL-21, initiate CLL proliferation in vitro and can be traced in CLL lymph node samples from patients [Pascutti et al., Blood 2013]. Targeting the underlying signaling pathways may be clinically relevant, and therefore we aimed to characterize the molecular mechanisms underlying antigen-independent proliferation. In the present study we applied CD40L/IL-21 stimulation to induce proliferation, and tested various specific kinase inhibitors for blocking potential. Surprisingly, the Btk inhibitor ibrutinib significantly suppressed CD40L/IL-21-induced proliferation (Figure 1). Similarly, inhibition of PI3Kδ with idelalisib dampened proliferation. While neither ibrutinib nor idelalisib affected CD40L-induced NF-kB or IL-21 induced STAT3 phosphorylation, both compounds efficiently blocked downstream ERK1/2 phosphorylation. Impact of idelalisib and ibrutinib was non-synergistic, suggesting that PI3K and Btk are acting in concert. In contrast with the inhibitory effects of the two compounds above, no effect of CD40L/IL-21 induced proliferation was observed following inhibition of SYK activity with R406 (tamatinib). This strongly suggests a role for PI3K and Btk signaling independent of BCR-signaling. We demonstrate that antigen-independent proliferation completely depends on downstream CDK4-activity, which can be blocked by the CDK4-inhibitor PD0332991. IL-21 signaling is absolutely required for antigen-independent proliferation as treatment with the pan-JAK inhibitor INCB abrogates proliferation. Moreover, immunohistochemical staining of lymph nodes from CLL patients indicated the presence of phospho-STAT3 in CLL cells at lymph node sites, suggesting a contribution of JAK/STAT signaling to in vivo proliferation. In conclusion, our data strongly suggest that non-BCR signals contribute to proliferation of CLL cells. Since the most recent clinical data point to development of resistance against ibrutinib, targeting non-BCR pathways may offer additional venues for treatment. Figure 1. CD40L/IL-21 induced proliferation can be inhibited with kinase inhibitors that target kinases involved in BCR-signaling Figure 1. CD40L/IL-21 induced proliferation can be inhibited with kinase inhibitors that target kinases involved in BCR-signaling Disclosures No relevant conflicts of interest to declare.

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Chen, Yongsheng, Liangjun Wei, Lichen Teng, Yan Cao, Dechao Li, Wentao Wang, Hongxin Pan, et al. "Camrelizumab combined with TIP (paclitaxel+cisplatin+ifosfamide) as neoadjuvant treatment of locally advanced penile cancer before lymphadenectomy: An exploratory, phase Ⅱ study." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): TPS5093. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.tps5093.

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TPS5093 Background: Penile squamous cell carcinoma (PSCC) is a highly aggressive disease that accounts for 95% of penile cancers and is characterized by a high risk of early locoregional spread and morbidity with subsequent potential for distant dissemination. The lymph node invasion is one of the most important factor that affects the prognosis of PSCC. Penile cancer patients with uninvolved inguinal lymph nodes had a 5-year survival rate of 66% compared with 27% for those with involvement, and penile cancer with the pelvic lymph node involvement have a worse 5-year survival rate that is typically less than 10%. Therefore, this study aims to reduce small lesions to reach the radical lymphadenectomy by camrelizumab combined with TIP in the neoadjuvant treatment of PSCC. Methods: In this single-arm, prospective, phase Ⅱ study, 34 patients with histological or cytological diagnosis of locally advanced PSCC (TX, N2-N3, M0), ECOG performance score of 0-1, planned to be recruited. Enrolled patients with inguinal and/or pelvic lymph node metastasis (positive percutaneous lymph node biopsy) after primary tumor resection of penile cancer were treated with combined therapy including camrelizumab (200 mg, iv, Q3W), paclitaxel (175 mg/m2, iv, Q3W), cisplatin (25 mg/m2, iv, Q3W) and ifosfamide (1200 mg/m2, iv, Q3W) for a total of 4 cycles. The primary endpoint is the rate of pathologic complete response (pCR). Secondary endpoints are event-free survival, overall survival, objective response rate, disease control rate and safety. On the basis of a threshold pCR rate of 13.6%, targeting an expected pCR of 34% and assuming 12 months follow-up, 80% power and a one-sided α = 0.05, this design requires 34 evaluable patients to be accrued over 3 years. Clinical trial information: ChiECRCT20210503.

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Manouilov, K. K., I. I. Fedorov, F. D. Boudinot, C. A. White, L. P. Kotra, R. F. Schinazi, Chung Hong, and Chung K. Chu. "Lymphatic Targeting of anti-HIV Nucleosides: Distribution of 3′-azido-3′-deoxythymidine (AZT) and 3′-azido-2′,3′-dideoxyuridine (AZdU) after Administration of Dipalmitoylphosphatidyl Prodrugs to Mice." Antiviral Chemistry and Chemotherapy 6, no. 4 (August 1995): 230–38. http://dx.doi.org/10.1177/095632029500600405.

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Human immunodeficiency virus appears to be proliferating within the lymphatic system throughout the period of clinical latency. Targeting of anti-HIV compounds to the lymphatic tissue may therefore provide therapeutic benefits. The purpose of this investigation was to determine the distribution of 3′-azido-3′-deoxythymidine (AZT) and 3′-azido-2′,3′-dideoxyuridine (AZdU) in lymph nodes in a mouse model after administration of the lipophilic prodrugs dipalmitoylphosphatidyl-azidodeoxythymidine (DPP-AZT) and dipalmitoylphosphatidyl-azidodideoxyuridine (DPP-AZdU). Mice received 50 mg kg−1 of parent nucleoside and 164 mg kg−1 of DPP-AZT (equivalent to 50 mg kg−1 AZT) intravenously or orally and 180mg kg−1 DPP-AZdU (equivalent to 50 mg kg−1 AZdU) orally. Serum, neck, axillary and mesenteric lymph nodes were collected at selected times and AZT and AZdU concentrations were determined by HPLC. The disposition of AZT and AZdU in serum and lymph nodes was significantly altered after intravenous and oral administration of DPP-AZT and oral administration of DPP-AZdU when compared to that after administration of parent nucleoside. Lower peak concentrations of AZT and AZdU were observed in serum and lymph nodes after administration of the phospholipid prodrugs. However, DPP-AZT and DPP-AZdU produced consistently higher concentrations of AZT and AZdU, respectively, 2-3 h after prodrug administration. Half-life values for both nucleosides in serum and lymph nodes were significantly greater after prodrug administration. Greater AUC values for nucleosides were noted in neck (AZT and AZdU) and mesenteric (AZT) lymph nodes after administration of prodrugs compared with values obtained for parent drugs. Furthermore, relative lymph node exposure to AZT and AZdU in the lymph nodes was greater after administration of prodrug than after administration of parent compound. Thus, DPP-AZT and DPP-AZdU show potential as useful prodrugs for the delivery of AZT and AZdU to the lymphatic system.

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Meena, Pushpa, Anjali Sharma, and Dalpat Meena. "Serum Lactate Dehydrogenase: A Possible Metabolomics Biomarker for the Early Detection of Head and Neck Cancer Lymph Node Metastasis." International Journal of Health Sciences and Research 12, no. 6 (June 24, 2022): 304–8. http://dx.doi.org/10.52403/ijhsr.20220639.

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Head and neck cancer (HNC) appears with one of the most recurring sites of cancer, and the percentage of metastases is also high in both localized region and distant areas. Diagnosis of metastases is correlated with poor prognosis, with a median survival of about 10 months. Therefore, early diagnosis is of utmost significance in the treatment of HNC. Metabolomics study targeting altered metabolic pathways exhibits a promising approach for discovering early novel noninvasive targets and biomarkers in HNC lymph node metastasis. An increased level of Lactate dehydrogenase (LDH) has been observed as a major diagnostic metabolomics biomarker for poor survival among HNC patients. It is also recommended as a more efficient biomarker of metastasis. For present study serum samples were collected from healthy controls (n=10) and HNC patients with and without lymph node metastasis (n=10 each). Prepared serum samples were analyzed by UV-spectrophotometer. Further, obtained data were analyzed using the one-way ANOVA test. Significant difference (p<0.05) was reported in the levels of serum metabolites between healthy control group and HNC lymph node metastasis (p<0.0006). Comprehensively, this study provides valuable insights in alteration of serum LDH enzyme level in early diagnosis and prediction of HNC. We proposed LDH could be used as an early metastasis biomarker in screening HNC lymph node metastasis patients. Key words:Head and neck cancer, Lymph node metastasis, Metabolomics, Lactate dehydrogenase (LDH), Serum .

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Mayer, Marcel, Lisa Nachtsheim, Franziska Hoffmann, Ferdinand von Eggeling, Orlando Guntinas-Lichius, Johanna Prinz, Jens Peter Klußmann, Alexander Quaas, Christoph Arolt, and Philipp Wolber. "CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target." International Journal of Molecular Sciences 23, no. 16 (August 12, 2022): 9037. http://dx.doi.org/10.3390/ijms23169037.

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Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman’s ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs.

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Dzhabarov, F. R., A. B. Alnikin, and V. G. Tolmachev. "Oligometastatic prostate cancer: diagnosis and preliminary results of radiation therapy." Urology Herald 8, no. 2 (July 1, 2020): 55–66. http://dx.doi.org/10.21886/2308-6424-2020-8-2-55-66.

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Prostate cancer (PCa) remains one of the most pressing problems of modern oncology, which is primarily associated with the high prevalence of this pathology. Of course, the appearance of metastases is an unfavourable factor in the course of the disease. However, PCa metastases is a very heterogeneous condition. «Oligometastatic cancer» is considered as a special disease with other properties of the tumour, i.e. as a transitional state between the localized and disseminated stage of the disease. Diagnosis of oligometastatic cancer is an extremely difficult task associated with the accurate determination of the number and localization of metastases, both hematogenous and lymphogenous, which in turn requires differentiation with regional lesions of the lymph nodes of a locally advanced tumour process. Currently, radiotracers are widely used to diagnose metastatic lymph node lesions that have high specificity for PCa, targeting a prostate-specific membrane antigen (PSMA; also known as glutamate carboxypeptidase), such as 11C-choline, 18F-fluoroethylcholine, 68Ga.9 patients with prostate cancer with the oligometastatic lesion were treated. All patients underwent external beam radiation therapy. Total focal dose on the visualized lymph collector of the affected lymph node amounted to 44.0 Gr. Total focal dose with the method of radiotherapy treatment «field in the field» on the node 70.0 Gr. In all patients, a PSA was reduced to a level below 1.0 ng/ml 6 weeks after completion of the course of radiation therapy and levelling the severity of adverse reactions. None of the treated patients showed signs of a PCa recurrence.

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Knitz, Michael W., Thomas E. Bickett, Laurel B. Darragh, Ayman J. Oweida, Shilpa Bhatia, Benjamin Van Court, Shiv Bhuvane, et al. "Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis." Journal for ImmunoTherapy of Cancer 9, no. 4 (April 2021): e001955. http://dx.doi.org/10.1136/jitc-2020-001955.

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BackgroundNumerous trials combining radiation therapy (RT) and immunotherapy in head and neck squamous cell carcinoma (HNSCC) are failing. Using preclinical immune cold models of HNSCC resistant to RT-immune checkpoint inhibitors, we investigate therapeutic approaches of overcoming such resistance by examining the differential microenvironmental response to RT.MethodsWe subjected two HPV-negative orthotopic mouse models of HNSCC to combination RT, regulatory T cells (Treg) depletion, and/or CD137 agonism. Tumor growth was measured and intratumorous and lymph node immune populations were compared among treatment groups. Human gene sets, genetically engineered mouse models DEREG and BATF3–/–, flow and time-of-flight cytometry, RNA-Seq, Treg adoptive transfer studies, and in vitro experiments were used to further evaluate the role of dendritic cells (DCs) and Tregs in these treatments.ResultsIn MOC2 orthotopic tumors, we find no therapeutic benefit to targeting classically defined immunosuppressive myeloids, which increase with RT. In these radioresistant tumors, supplementing combination RT and Treg depletion with anti-CD137 agonism stimulates CD103+ DC activation in tumor-draining lymph nodes as characterized by increases in CD80+ and CCR7+ DCs, resulting in a CD8 T cell-dependent response. Simultaneously, Tregs are reprogrammed to an effector phenotype demonstrated by increases in interferonγ+, tumor necrosis factorα+, PI3K+, pAKT+ and Eomes+ populations as well as decreases in CTLA4+ and NRP-1+ populations. Tumor eradication is observed when RT is increased to an 8 Gy x 5 hypofractionated regimen and combined with anti-CD25+ anti-CD137 treatment. In a human gene set from oral squamous cell carcinoma tumors, high Treg number is associated with earlier recurrence.ConclusionsRegulating Treg functionality and DC activation status within the lymph node is critical for generating a T cell effector response in these highly radioresistant tumors. These findings underscore the plasticity of Tregs and represent a new therapeutic opportunity for reprogramming the tumor microenvironment in HNSCCs resistant to conventional radioimmunotherapy approaches.

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Bourquin, Carole, David Anz, Klaus Zwiorek, Anna-Lisa Lanz, Sebastian Fuchs, Sarah Weigel, Cornelia Wurzenberger, et al. "Targeting CpG Oligonucleotides to the Lymph Node by Nanoparticles Elicits Efficient Antitumoral Immunity." Journal of Immunology 181, no. 5 (August 19, 2008): 2990–98. http://dx.doi.org/10.4049/jimmunol.181.5.2990.

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Nishimoto, Yutaka, Shu Nagashima, Kohei Nakajima, Takayuki Ohira, Tatsumi Sato, Takeshi Izawa, Jyoji Yamate, et al. "Carboxyl-, sulfonyl-, and phosphate-terminal dendrimers as a nanoplatform with lymph node targeting." International Journal of Pharmaceutics 576 (February 2020): 119021. http://dx.doi.org/10.1016/j.ijpharm.2020.119021.

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Bobek, Vladimir, Katarina Kolostova, Daniela Pinterov, Michael Boubelik, Ping Jiang, Meng Yang, and Robert M. Hoffman. "Syngeneic lymph-node-targeting model of green fluorescent protein-expressing Lewis lung carcinoma." Clinical & Experimental Metastasis 21, no. 8 (May 18, 2005): 705–8. http://dx.doi.org/10.1007/s10585-004-8118-8.

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Liu, Hong, Zhenfu Wen, Haolin Chen, Zeyu Yang, Zhicheng Le, Zhijia Liu, Yongming Chen, and Lixin Liu. "Nanoadjuvants Actively targeting lymph node conduits and blocking tumor invasion in lymphatic vessels." Journal of Controlled Release 352 (December 2022): 497–506. http://dx.doi.org/10.1016/j.jconrel.2022.10.053.

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Press, Michael F., Peter H. O'Donnell, Elizabeth R. Plimack, Leonard G. Gomella, David I. Quinn, Padmanee Sharma, Todd DeVries, Robert Brownell Sims, Melissa Chen, and Dean F. Bajorin. "HER2 expression in patients (pts) with surgically resected urothelial cancer at high risk of recurrence screened for the phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy targeting HER2." Journal of Clinical Oncology 31, no. 6_suppl (February 20, 2013): 292. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.292.

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292 Background: HER2 overexpression has been suggested as a poor prognostic factor in pts with high-risk urothelial carcinoma (UC). Published data note a wide range of HER2 overexpression in UC, with some reports showing <10% of cases and others exhibiting >50% of cases with ≥2+ HER2 expression by immunohistochemistry (IHC). NeuACT (N10-1; NCT01353222) is a phase 2 trial to determine whether DN24-02, an autologous cellular immunotherapy targeting HER2 based on the same platform used for sipuleucel-T, given as adjuvant therapy following surgical resection can prolong survival (Bajorin, et al. ASCO 2012). Here we report preliminary data for HER2 expression on primary tumor and positive lymph node samples from this study. Methods: Trial eligibility criteria include surgical resection of a primary UC, with either ≥pT2 or pN+ staging, and HER2 expression ≥1+ IHC. Surgical specimens are screened for HER2 expression by central pathology laboratory review and HER2 positivity is scored using the Dako HercepTest scoring system. Results: As of August 2012, tumor specimens from 61 pts have been screened for HER2 expression. Of these pts, 49 (80%; 95% CI: 68–89%) had a HER2 expression score of ≥1+ in the primary tumor, with 27 (44%) having ≥2+ score and 3 (5%) having a 3+ score. Twenty-three pts (38%) also had HER2 expression levels evaluated in tumor from involved lymph nodes. A total of 20 (87%; 95% CI: 66–97%) of these pts had a HER2 expression score of ≥1+ in the lymph nodes, with 12 (52%) having a ≥2+ score and 3 (15%) having a 3+ score. Two pts had primary tumor samples that expressed HER2 but were negative for HER2 expression in the lymph nodes submitted for analysis. Conclusions: Although preliminary, a high frequency (≥80%) of HER2 expression score of ≥1+ in primary tumor and lymph node samples was observed. These data highlight the prevalence of HER2 protein expression in high-risk UC. Furthermore, the HER2 expression data are consistent with previously published data in pts with invasive UC. Clinical trial information: NCT01353222.

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Tonkin, Daniel, Mario Barro, and Robert Johnston. "Interplay of alphavirus-based replicons with dendritic cells induces innate immune activation and enhances adaptive immunity (53.1)." Journal of Immunology 188, no. 1_Supplement (May 1, 2012): 53.1. http://dx.doi.org/10.4049/jimmunol.188.supp.53.1.

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Abstract Venezuelan equine encephalitis virus replicon particles (VRP) are infectious, non-propagating particles which function as a safe and robust humoral, mucosal and cellular adjuvant when codelivered with antigen. VRP are known to infect dendritic cells (DCs) in vitro and in vivo, and we have explored the role of DCs in the adjuvant activity of VRP. Upon footpad injection VRP are rapidly transported to the draining lymph node, resulting in cytokine secretion and recruitment of leukocytes. We found that DCs were preferentially infected in the lymph node, although other cell types were also infected. TNF-secreting monocyte-derived inflammatory DCs were the cell type most dramatically recruited to the lymph node and also the most readily infected by VRP. These inflammatory DCs also efficiently took up antigen. By depletion of DCs we demonstrated that both VRP transport to the lymph node and the subsequent inflammatory response were at least partly DC-dependent. By in vitro analysis we found that VRP-infected DCs can amplify CD4 and CD8 T cell responses to antigen, which is mediated at least partly by DC-secreted factors. We also show that VRP-infected DCs are sufficient generate an adjuvant effect comparable to that achieved by injection of VRP alone. Altogether, these data provide strong evidence that in vivo targeting of DCs by VRP matures and alters those DCs in a manner that potentiates the adjuvant activity of VRP.

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Chen, Feng, Brian Madajewski, Kai Ma, Daniella Karassawa Zanoni, Hilda Stambuk, Melik Z. Turker, Sébastien Monette, et al. "Molecular phenotyping and image-guided surgical treatment of melanoma using spectrally distinct ultrasmall core-shell silica nanoparticles." Science Advances 5, no. 12 (December 2019): eaax5208. http://dx.doi.org/10.1126/sciadv.aax5208.

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Accurate detection and quantification of metastases in regional lymph nodes remain a vital prognostic predictor for cancer staging and clinical outcomes. As intratumoral heterogeneity poses a major hurdle to effective treatment planning, more reliable image-guided, cancer-targeted optical multiplexing tools are critically needed in the operative suite. For sentinel lymph node mapping indications, accurately interrogating distinct molecular signatures on cancer cells in vivo with differential levels of sensitivity and specificity remains largely unexplored. To address these challenges and demonstrate sensitivity to detecting micrometastases, we developed batches of spectrally distinct 6-nm near-infrared fluorescent core-shell silica nanoparticles, each batch surface-functionalized with different melanoma targeting ligands. Along with PET imaging, particles accurately detected and molecularly phenotyped cancerous nodes in a spontaneous melanoma miniswine model using image-guided multiplexing tools. Information afforded from these tools offers the potential to not only improve the accuracy of targeted disease removal and patient safety, but to transform surgical decision-making for oncological patients.

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Yang, Xiqin, Tong Yu, Yingping Zeng, Keke Lian, Xueqing Zhou, Sufen Li, Guoxi Qiu, Xiangyu Jin, Hong Yuan, and Fuqiang Hu. "Tumor-draining lymph node targeting chitosan micelles as antigen-capturing adjuvants for personalized immunotherapy." Carbohydrate Polymers 240 (July 2020): 116270. http://dx.doi.org/10.1016/j.carbpol.2020.116270.

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Yu, Dan, Guang-Hong Han, Xue Zhao, Xueshibojie Liu, Kai Xue, Di Wang, and Cheng-Bi Xu. "MicroRNA-129-5p suppresses nasopharyngeal carcinoma lymphangiogenesis and lymph node metastasis by targeting ZIC2." Cellular Oncology 43, no. 2 (December 28, 2019): 249–61. http://dx.doi.org/10.1007/s13402-019-00485-5.

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Kawasato, Karina Hatamoto, Léa Campos de Oliveira, Paulo Eduardo Neves Ferreira Velho, Lidia Yamamoto, Gilda Maria Barbaro Del Negro, and Thelma Suely Okay. "Detection of Bartonella henselae DNA in clinical samples including peripheral blood of immune competent and immune compromised patients by three nested amplifications." Revista do Instituto de Medicina Tropical de São Paulo 55, no. 1 (February 2013): 1–6. http://dx.doi.org/10.1590/s0036-46652013000100001.

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Bacteria of the genus Bartonella are emerging pathogens detected in lymph node biopsies and aspirates probably caused by increased concentration of bacteria. Twenty-three samples of 18 patients with clinical, laboratory and/or epidemiological data suggesting bartonellosis were subjected to three nested amplifications targeting a fragment of the 60-kDa heat shock protein (HSP), the internal transcribed spacer 16S-23S rRNA (ITS) and the cell division (FtsZ) of Bartonella henselae, in order to improve detection in clinical samples. In the first amplification 01, 04 and 05 samples, were positive by HSP (4.3%), FtsZ (17.4%) and ITS (21.7%), respectively. After the second round six positive samples were identified by nested-HSP (26%), eight by nested-ITS (34.8%) and 18 by nested-FtsZ (78.2%), corresponding to 10 peripheral blood samples, five lymph node biopsies, two skin biopsies and one lymph node aspirate. The nested-FtsZ was more sensitive than nested-HSP and nested-ITS (p < 0.0001), enabling the detection of Bartonella henselae DNA in 15 of 18 patients (83.3%). In this study, three nested-PCR that should be specific for Bartonella henselae amplification were developed, but only the nested-FtsZ did not amplify DNA from Bartonella quintana. We conclude that nested amplifications increased detection of B. henselae DNA, and that the nested-FtsZ was the most sensitive and the only specific to B. henselae in different biological samples. As all samples detected by nested-HSP and nested-ITS, were also by nested-FtsZ, we infer that in our series infections were caused by Bartonella henselae. The high number of positive blood samples draws attention to the use of this biological material in the investigation of bartonellosis, regardless of the immune status of patients. This fact is important in the case of critically ill patients and young children to avoid more invasive procedures such as lymph nodes biopsies and aspirates.

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Hauke, R. J., and C. Enke. "Phase I study of extended field intensity modulated radiation therapy (EF-IMRT) and docetaxel in patients with node-positive prostate cancer." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e16154-e16154. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16154.

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e16154 Background: Treatment for patients with node positive prostate cancer remains challenging. With hormonal ablation therapy (HAT), conventional radiation doses to the lymph nodes produces few cures or long-term remissions, likely due to suboptimal doses and/or fields of radiation. Docetaxel has radiosensitizing properties. We conducted a phase I study combining HAT with EF-IMRT and concurrent docetaxel in men with biopsy-proven node positive prostate cancer. Methods: Eligible patients had biopsy proven N1M0 disease and adequate hematologic and hepatic function. All subjects received neoadjuvant HAT (bicalutamide 50 mg/d with an LHRH agonist) for at least 2 months but less than 13 months prior to EF-IMRT and continued for 2 years after completion of radiation (bicalutamide discontinued at the end of radiation). EF-IMRT target doses: prostate 81.0 Gy/45 fractions; intraprostatic target 81.0 - 84.6 Gy/45 fractions; pathologically involved lymph node 72 Gy/43 fractions; pelvic lymph nodes 54.0 Gy to 70.2 Gy/43 fractions. Ultrasound targeting and a water filled rectal catheter balloon were used daily to minimize movement and locate the prostate. Weekly docetaxel was administered during radiation at 5, 10 or 17 mg/m2. The primary endpoint was determining grade III/IV toxicity. Results: Nine patients have been treated. No grade III/IV toxicities occurred within the defined observation period. All subjects received their prescribed radiation and chemotherapy doses. One patient developed an anal fissure and one patient had tachyarrhythmias about 6 months after radiation. Seven of 9 patients are now beyond the 2 year post-radiation period; 4 patients remain in remission; one patient developed primary lung cancer; another was lost to follow up at 1 year post-radiation and 3 had relapsed disease within the 2 year post-radiation window. Conclusions: The addition of weekly docetaxel to EF-IMRT along with HAT is well tolerated in patients with node positive prostate cancer. Phase II studies are warranted based on these results. [Table: see text]

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Journal articles on the topic 'Lymph node targeting'

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