Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy

作者：Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami‐Chouaib · 发表于：Frontiers in Immunology · 年份：2018 · DOI：10.3389/fimmu.2018.00014 · 被引用次数：525 · 研究领域：CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses

Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including CTLA-4 and PD-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies (mAb) have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma (NSCLC). PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I (MHC-I)/beta-2-microglobulin (beta2m) complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B. T-cell adhesion molecules and, in particular, lymphocyte-function-associated antigen-1 (LFA-1) and CD103 integrins, and their cognate ligands, respectively, intercellular adhesion molecule 1 (ICAM-1) and E-cadherin, on target cells, are involved in strengthening the interaction between CTL and tumor cells. Tumor-specific CTL have been isolated from tumor-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) of patients with varied cancers. TCRbeta-chain gene usage indicated that CTL identified in vitro selectively expanded in vivo at the tumor site compared to autologous PBL. Moreover, functional studies indicated that these...