Intratumoral CD8⁺ T-cell Apoptosis Is a Major Component of T-cell Dysfunction and Impedes Antitumor Immunity.

ABSTRACT: Subsets of human tumors are infiltrated with tumor antigen-specific CD8⁺ T cells [tumor-infiltrating lymphocytes (TILs)] despite tumor progression. These TILs are thought to be inactivated by the immunosuppressive tumor microenvironment, through the engagement of inhibitory receptors such as CTLA-4 and PD-1. However, antigen-specific CD8⁺ TILs are not functionally inert but are undergoing activation in situ Here, we show that antigen-specific CD8⁺ TILs are actively proliferating, yet also undergo high rates of apoptosis, leading to a vicious cycle of activation and death that limits immune efficacy. Preventing CD8⁺ TIL apoptosis by Bcl-x_L overexpression enabled accumulation and improved tumor control. Effective combination immun

SUBMITTER: Horton BL 

PROVIDER: S-EPMC5754226 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature