Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8+ T cells.
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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.
author list (cited authors)
Das, J. K., Ren, Y., Kumar, A., Peng, H., Wang, L., Xiong, X., ... Song, J.
complete list of authors
Das, Jugal Kishore||Ren, Yijie||Kumar, Anil||Peng, Hao-Yun||Wang, Liqing||Xiong, Xiaofang||Alaniz, Robert C||de Figueiredo, Paul||Ren, Xingcong||Liu, Xiaoqi||Ryazonov, Alexey G||Yang, Jin-Ming||Song, Jianxun