Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8 <sup>+</sup> T cells
Jugal Kishore Das, Yijie Ren, Anil Kumar, Hao‐Yun Peng, Liqing Wang, Xiaofang Xiong, Robert C. Alaniz, Paul de Figueiredo, Xingcong Ren, Xiaoqi Liu, Alexey G. Ryazonov, Jinming Yang, Jianxun Song
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 + T cells. Thus, eEF-2K is critically required for sustaining the viability and function of cytotoxic CD8 + T cells, and therapeutic augmentation of this kinase may be exploited as a novel approach to reinforcing CAR-T therapy against cancer.