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A point mutation in the NFYC gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human squamous cell lung carcinoma. CD8+ T cells have important roles in antitumor immunity (1, 7), some of which are dependent upon the Notch pathway. doi:10.1126/scitranslmed.3008211, 123. Identification of a mutated receptor-like protein tyrosine phosphatase kappa as a novel, class II HLA-restricted melanoma antigen. Where are we going? 2015 Apr 2;520(7545):57-62. doi: 10.1038/nature14344. IFNγ sensitizes tumor cells to…, Figure 2. doi:10.1146/annurev-immunol-032713-120136, 132. Competing interests GG and ES are inventors on intellectual property related to cyst(e)inase and hold equity interest in Aeglea Biotherapeutics Inc. TAC is a co-founder of Gritstone Oncology and holds equity. doi: 10.1158/2159-8290.CD-NB2019-058. Recent accessibility to next-generation sequencing (NGS) technology and improvement in in silico epitope prediction have contributed to identification of patient-specific tumor antigens generated by somatic mutations in individual tumors (Table 3). doi:10.1073/pnas.92.17.7976. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. June CH. doi:10.1038/nri2526, 16. Epub 2018 Jul 26. doi:10.1038/nrc3670, 47. In our study, the elevated expression of CD39 in CD4+/CD8+ T cells were significantly associated with the pathological T stage (pT < 2, P = 0.041) and papillary tumor (P = 0.038). More recently, it has been shown that CD4+ T-cell help optimized CTL in expression of cytotoxic effector molecules, downregulation of inhibitory receptors, and increased migration capacities (31). Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Zorn E, Hercend T. A natural cytotoxic T cell response in a spontaneously regressing human melanoma targets a neoantigen resulting from a somatic point mutation. To further improve their antitumor effectiveness, and for more robust long-term disease control, a deeper understanding of host-tumor interactions and tumor immune escape strategies is required. Chiari R, Foury F, De Plaen E, Baurain JF, Thonnard J, Coulie PG. TAC acknowledges grant funding from Bristol-Myers Squibb, AstraZeneca, Illumina, Pfizer, An2H, and Eisai. Clin Cancer Res (2011) 17(13):4550–7. They are heterogeneous in nature and were classified into at least four groups according to their expression repertoire and the source of the antigen: antigens encoded by cancer-germline genes, differentiation antigens, overexpressed antigens, and viral antigens (Table 1). Several of them recognize truly tumor-specific antigens encoded by mutated genes, also known as neoantigens, which likely play a key role in antitumor CD8 T-cell immunity. The role of IFNs in cancer and in response to therapy is similarly complex. Adhesion/costimulatory molecules, mainly lymphocyte-function-associated antigen-1 (LFA-1, CD11a/CD18 or αL/β2) and CD103 (αE/β7) integrins, on CTL play a critical role in TCR-mediated killing by interacting with their cognate ligands, intercellular adhesion molecule 1 (or CD54) and E-cadherin, respectively, and directing exocytosis of lytic granules to the cancer cell surface at the IS (2, 3). Nat Med (1997) 3(6):682–5. 66. Baitsch L, Baumgaertner P, Devevre E, Raghav SK, Legat A, Barba L, et al.

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