IL-9/STAT3/fatty acid oxidation-mediated lipid peroxidation contributes to Tc9 cell longevity and enhanced antitumor activity.

ABSTRACT: CD8+ T cell longevity regulated by metabolic activity plays important roles in cancer immunotherapy. Although in vitro-polarized, transferred IL-9-secreting CD8+ Tc9 (cytotoxic T lymphocyte subset 9) cells exert greater persistence and antitumor efficacy than Tc1 cells, the underlying mechanism remains unclear. Here, we show that tumor-infiltrating Tc9 cells display significantly lower lipid peroxidation than Tc1 cells in several mouse models, which is strongly correlated with their persistence. Using RNA-sequence and functional validation, we found that Tc9 cells exhibited unique lipid metabolic programs. Tc9 cell-derived IL-9 activated STAT3, upregulated fatty acid oxidation and mitochondrial activity, and rendered Tc9 cells with reduced lipid peroxidation and resistance to tumor- or ROS

SUBMITTER: Xiao L 

PROVIDER: S-EPMC8970676 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature