NAD+NAD+ potentiates killing tumors in tumor-infiltrated T cells

Moyvore
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Joined: Mon Sep 16, 2019 8:38 pm

NAD+ potentiates killing tumors in tumor-infiltrated T cells

Post by Moyvore »

Cell Rep2021 Aug 10
NAD+ supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells

"...
 Excitingly, both adoptive CAR-T and anti-PD1 immune checkpoint blockade mouse models demonstrate that NAD+ supplementation enhanced the tumor-killing efficacy of T cells.

Collectively, this study reveals that an impaired TCR-TUB-NAMPT-NAD+ axis leads to T cell dysfunction in the tumor microenvironment, and an over-the-counter nutrient supplement of NAD+ could boost T-cell-based immunotherapy."


Abstract:
https://pubmed.ncbi.nlm.nih.gov/34380043/


The full 22-page pdf includes:

"...Detailed LC-MS data further revealed decreased levels of intermediate metabolites in both metabolic pathways upon FK866 treatment, including lactate, citric acid, succinic acid, and oxoglutaric acid (Figure S4E), and this reduction could be fully rescued by addition of exogenous NAD+ (Figure S4E). Furthermore, we applied a glycolytic stress test to monitor the effect of inhibitors and NAD+ on aerobic glycolysis. By comparing 3 stages of T cells, namely, (1) naive T cells; (2) primed T cells, which are naive T cells with 24-h stimulation; and (3) effector T cells, which are expanded T cells, we found that FK866 showed the most robust inhibition of glycolysis in effector T cells (Figure 3C). Together, these results indicated that NAD+ depletion caused systematic metabolic defects in T cells, featured with glycolysis within the cytosol and the citric acid cycle within mitochondria."