Mitochondrial metabolic flexibility is critical for CD8⁺ T cell antitumor immunity.

ABSTRACT: Mitochondria use different substrates for energy production and intermediatory metabolism according to the availability of nutrients and oxygen levels. The role of mitochondrial metabolic flexibility for CD8⁺ T cell immune response is poorly understood. Here, we report that the deletion or pharmacological inhibition of protein tyrosine phosphatase, mitochondrial 1 (PTPMT1) significantly decreased CD8⁺ effector T cell development and clonal expansion. In addition, PTPMT1 deletion impaired stem-like CD8⁺ T cell maintenance and accelerated CD8⁺ T cell exhaustion/dysfunction, leading to aggravated tumor growth. Mechanistically, the loss of PTPMT1 critically altered mitochondrial fuel selection-the utilization of pyruvate, a major mitochondrial

SUBMITTER: Chen C 

PROVIDER: S-EPMC10699783 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature