biostudies-literatureDas JKNIAID NIH HHSNCI NIH HHSeabl9783https://www.ebi.ac.uk/biostudies/studies/S-EPMC8809536biostudies-literatureUnknown8(5)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<sup>+</Science advancesElongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8⁺ T cells.PMC8809536R01 CA221867R01 AI121180R21 AI167793R21 AI128325Ren XRen YPeng HYYang JMSong JWang LXiong XLiu XRyazonov AGde Figueiredo PAlaniz RCKumar ADas JKfalseElongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8⁺ T cells.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<sup>+</2022-01-01T00:00:00Z2022 Feb2026-06-04T04:37:44.405Z2024-10-16T10:39:26.234ZS-EPMC88095363510804410.1126/sciadv.abl9783