CD36-mediated ferroptosis dampens intratumoral CD8⁺ T cell effector function and impairs their antitumor ability.

ABSTRACT: Understanding the mechanisms underlying how T cells become dysfunctional in a tumor microenvironment (TME) will greatly benefit cancer immunotherapy. We found that increased CD36 expression in tumor-infiltrating CD8⁺ T cells, which was induced by TME cholesterol, was associated with tumor progression and poor survival in human and murine cancers. Genetic ablation of Cd36 in effector CD8⁺ T cells exhibited increased cytotoxic cytokine production and enhanced tumor eradication. CD36 mediated uptake of fatty acids by tumor-infiltrating CD8⁺ T cells in TME, induced lipid peroxidation and ferroptosis, and led to reduced cytotoxic cytokine production and impaired antitumor ability. Blocking CD36 or inhibiting ferroptosis in CD8⁺ T cells effectively res

SUBMITTER: Ma X 

PROVIDER: S-EPMC8102368 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature