ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression.

ABSTRACT: Understanding the intrinsic mediators that render CD8⁺ T cells dysfunctional in the tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report that C/EBP homologous protein (Chop), a downstream sensor of severe endoplasmic reticulum (ER) stress, is a major negative regulator of the effector function of tumor-reactive CD8⁺ T cells. Chop expression is increased in tumor-infiltrating CD8⁺ T cells, which correlates with poor clinical outcome in ovarian cancer patients. Deletion of Chop in T cells improves spontaneous antitumor CD8⁺ T cell immunity and boosts the efficacy of T cell-based immunotherapy. Mechanistically, Chop in CD8⁺ T cells is elevated primarily through the ER stress-associated

SUBMITTER: Cao Y 

PROVIDER: S-EPMC6426975 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature