Methionine regulates antitumor function of CD8⁺ T cells through polyamine synthesis.

ABSTRACT: Methionine is an essential amino acid critical for T cell activation. While methionine restriction (MR) combined with immune checkpoint blockade has been shown to enhance T cell function, the impact of methionine on adoptive T cell therapies is largely unexplored. Here, we examined the functionality of T cells under MR and pharmaceutical inhibition of the methionine cycle (MAT2Ai), using primary T cells and a murine adoptive T cell therapy model. In vitro, transient MR or MAT2Ai treatment increased interferon gamma (IFNγ) expression in CD8⁺ T cells, whereas sustained MR led to the upregulation of T cell exhaustion-associated markers. Mechanistically, transient MR suppressed the polyamine synthesis pathway, and supplementation with polyamines reversed MR-induced IFNγ expre

SUBMITTER: Zhao T 

PROVIDER: S-EPMC12621867 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature