Elongation factor-2 kinase is a critical determinant of the fate and antitumor immunity of CD8+ 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, Jin Ming Yang, Jianxun Song

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbereabl9783
JournalScience advances
Volume8
Issue number5
DOIs
StatePublished - Feb 2022

Bibliographical note

Funding Information:
We thank S.-H. Chen at the Houston Methodist Research Institute for the imaging mass cytometry analysis. This work was supported by NIH grants R01CA221867 (to J.-M.Y. and J.S.), R01AI121180, and R21AI128325 and Department of Defense grant LC210150 (to J.S.)

Publisher Copyright:
Copyright © 2022 The Authors,

ASJC Scopus subject areas

  • General

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