Researchers introduced a resection and response-assessment approach for studying the tumor microenvironment before or shortly after treatment initiation to identify predictive biomarkers differentiating responders from nonresponders.
[Proceedings of the National Academy of Sciences of the United States of America]
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Chen, I. X., Newcomer, K., Pauken, K. E., Juneja, V. R., Naxerova, K., Wu, M. W., Pinter, M., Sen, D. R., Singer, M., Sharpe, A. H., & Jain, R. K. (2020). A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2002806117 Cite
Collagen-induced T cell exhaustion occured through the receptor LAIR1, which is upregulated following CD18 interaction with collagen, and induces T cell exhaustion through SHP-1.
The authors revealed that genetically targeting the autophagy-related protein PIK3C3/VPS34 in melanoma and colorectal tumor cells, or treating tumor-bearing mice with selective inhibitors of the PIK3C3/VPS34 kinase activity, reprograms cold immune desert tumors into hot, inflamed immune infiltrated tumors.
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Dual immunofluorescence using CD33 and VISTA antibodies was performed. VISTA expression positively correlated with CD33 expression in melanoma tissue.
Repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes of mice due to recruitment and accumulation of macrophages via the CD8+ T cell-IFN-γ axis.
[Cellular & Molecular Immunology]
Investigators showed that the frequency of programmed cell death protein 1 (PD-1)+CD8+ T cells relative to that of PD-1+ regulatory T cells in the tumor microenvironment could predict the clinical efficacy of PD-1 blockade therapies and is superior to other predictors, including PD ligand 1 expression or tumor mutational burden.
ImmunoGenesis, Inc. announced that it has been awarded a $15.5 M grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to advance development of IMGS-001, the company’s dual specific Checkpoint Inhibitor and Tumor Microenvironment (TME) remodeling agent. IMGS-001, through its mechanism of action, has the potential to provide superior blockade of the PD-1 pathway and clear out immunosuppressive elements in the TME. This ability to remodel the TME to a more immune supportive environment is believed to be a critical factor in facilitating efficacy in immunologically “cold” cancers such as prostate, colorectal and pancreatic cancer.
Investigators demonstrated interleukin 32 (IL-32) expression in human melanoma positively correlated with overall survival, response to immune checkpoint blockade, and an immune inflamed tumor microenvironment enriched in mature dendritic cells, M1 macrophages and CD8+ T cells.
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Gruber, T., Kremenovic, M., Sadozai, H., Rombini, N., Baeriswyl, L., Maibach, F., Modlin, R. L., Gilliet, M., Werdt, D. V., Hunger, R. E., Parisi, G., Abril-Rodriguez, G., Ribas, A., & Schenk, M. (2020). IL-32γ potentiates tumor immunity in melanoma. JCI Insight. https://doi.org/10.1172/jci.insight.138772 Cite
The authors demonstrated that the CoV-2 specific CD4+ T-helper cell response was directed against all three proteins with comparable magnitude, ex vivo proliferation and portions of responding patients.
[Journal of Clinical Oncology]
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Sattler, A., Angermair, S., Stockmann, H., Heim, K. M., Khadzhynov, D., Treskatsch, S., Halleck, F., Kreis, M. E., & Kotsch, K. (2020). SARS-CoV-2 specific T-cell responses and correlations with COVID-19 patient predisposition. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI140965 Cite
Investigators report that PD-L1 translocated from the plasma membrane into the nucleus through interactions with components of the endocytosis and nucleocytoplasmic transport pathways, regulated by p300-mediated acetylation and HDAC2-dependent deacetylation of PD-L1.
[Nature Cell Biology]
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Gao, Y., Nihira, N. T., Bu, X., Chu, C., Zhang, J., Kolodziejczyk, A., Fan, Y., Chan, N. T., Ma, L., Liu, J., Wang, D., Dai, X., Liu, H., Ono, M., Nakanishi, A., Inuzuka, H., North, B. J., Huang, Y.-H., Sharma, S., … Wei, W. (2020). Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nature Cell Biology, 1–12. https://doi.org/10.1038/s41556-020-0562-4 Cite
Scientists report that maganese was essential in innate immune sensing of tumors and enhanced adaptive immune responses against tumors.
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Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy | Cell Research. (n.d.). Retrieved August 24, 2020, from https://www.nature.com/articles/s41422-020-00395-4 Cite