| 论文作者 |
Yao, CC; Sun, RM; Yang, Y; Zhou, HY; Meng, ZW; Chi, R; Xia, LL; Ji, P; Chen, YY; Zhang, GQ; Sun, HP; Lu, S; Yang, C; Wang, Y |
| 摘要 |
Branched-chain amino acids (BCAAs) provide nutrient signals for cell survival and growth. How BCAAs affect CD8+ T cell functions remains unexplored. Herein, we report that accumulation of BCAAs in CD8+ T cells due to the impairment of BCAA degradation in 2C-type serine/threonine protein phosphatase (PP2Cm)-deficient mice leads to hyper-activity of CD8+ T cells and enhanced anti-tumor immunity. CD8+ T cells from PP2Cm-/-mice upregulate glucose transporter Glut1 expression in a FoxO1-dependent manner with more glucose up-take, as well as increased glycolysis and oxidative phosphorylation. Moreover, BCAA supplementation reca-pitulates CD8+ T cell hyper-functions and synergizes with anti-PD-1, in line with a better prognosis in NSCLC patients containing high BCAAs when receiving anti-PD-1 therapy. Our finding thus reveals that accumula-tion of BCAAs promotes effector function and anti-tumor immunity of CD8+ T cells through reprogramming glucose metabolism, making BCAAs alternative supplementary components to increase the clinical efficacy of anti-PD-1 immunotherapy against tumors. |
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