Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8⁺ T cells.

ABSTRACT: eEF-2K has important roles in stress responses and cellular metabolism. We report here a previously unappreciated but critical role of eEF-2K in regulating the fate and cytocidal activity of CD8⁺ T cells. CD8⁺ T cells from eEF-2K KO mice were more proliferative but had lower survival than their wild-type counterparts after their activation, followed by occurrence of premature senescence and exhaustion. eEF-2K KO CD8⁺ T cells were more metabolically active and showed hyperactivation of the Akt-mTOR-S6K pathway. Loss of eEF-2K substantially impaired the activity of CD8⁺ T cells. Furthermore, the antitumor efficacy and tumor infiltration of the CAR-CD8⁺ T cells lacking eEF-2K were notably reduced as compared to the control CAR-CD8^+</

SUBMITTER: Das JK 

PROVIDER: S-EPMC8809536 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature