Cytotoxic CD8+ Lymphocytes in the Tumor Microenvironment

AbstractIn the tumor microenvironment, CD8+ T cells play a major role in tumor immunity. CD8+ T cells differentiate to cytotoxic T cells, traffic into the tumor microenvironment, and exhibit cytotoxicity against tumor cells. These processes have both positive and negative effects. Enhancements in the cytotoxic activity of tumor antigen-specific cytotoxic T cells in the tumor microenvironment are crucial for the development of cancer immunotherapy. To achieve this, several immunotherapies, including cancer vaccines, T cells engineered to express chimeric antigen receptors (CAR T cells), and bispecific T-cell engagers (BiTEs), have been developed. In contrast to cancer vaccines, CAR T cells, and BiTEs, immune checkpoint inhibitors enhance the activity of cytotoxic T cells by inhibiting the negative regulators of T cells.The total number, type, and activity of tumor antigen-specific cytotoxic T cells in the tumor microenvironment need to be clarified, particularly for the development of companion diagnostics to identify patients for whom these therapies are effective. Therefore, technologies including TCR repertoire, single-cell, and T-cell cytotoxicity analyses using BiTEs have been developed.Based on these and future innovations, the generation of effective cancer immunotherapies is anticipated.KeywordsCytotoxic T cellsCD8+ T cellsTumor microenvironmentT-cell receptorT-cell cytotoxicityTumor-specific antigenNeoantigenT-cell exhaustionT-cell metabolismImmune checkpoint inhibitorPD-1PD-L1CTLA-4Tumor mutation burdenBispecific T-cell engager