NAD+ supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells

• DOI: 10.1016/j.celrep.2021.109516
• Publication Date: 2021-08-10T16:05:31Z
• Authors: Yuetong Wang; Fei Wang; Lihua Wang; Shizhen Qiu; Yufeng Yao; Chenxu Yan; Xuexue Xiong; Xuyong Chen; Quanquan Ji; Jian Cao; Ganglong Gao; Dake Li; Liye Zhang; Zhiqian Guo; Ruoning Wang; Haopeng Wang; Gaofeng Fan
• Keywords: Nicotinamide phosphoribosyltransferase; Immune checkpoint

Although tumor-infiltrating lymphocytes (TILs) maintain their ability to proliferate, persist, and eradicate tumors, they are frequently dysfunctional in situ. By performing both whole-genome CRISPR metabolic inhibitor screens, we identify that nicotinamide phosphoribosyltransferase (NAMPT) is required for T cell activation. NAMPT low TILs, its expression controlled by the transcriptional factor Tubby (TUB), whose activity depends on receptor-phospholipase C gamma (TCR-PLCγ) signaling axis. The intracellular level of NAD