| 论文作者 |
Wang, FX; Bao, RJ; Xu, SY; Li, WY; Huang, HY; Li, RC; Ding, XY; Zhang, YR; Yu, XY; Han, QQ; Du, X; Wan, J; Li, S; Xiao, YC; Zhao, R; Cui, XG; Ye, YQ; Sun, JY; Zheng, JK; Chen, GQ; Zou, Q |
| 摘要 |
T cell dysfunction with age underlies an increased incidence of cancer in elderly individuals; however, how T cell aging is triggered in the tumor microenvironment is unclear. Here, we show that an age-associated reduction in adipocyte-derived leptin contributes to the accumulation of tumor-infiltrating senescent CD8+ T cells. Single-cell profiling of human and mouse cancer tissues reveals that the frequency of intratumoral senescent CD8+ T cells increases with age, leading to a weak antitumor effect. Moreover, decreased levels of adipocyte-derived leptin are an indispensable factor for CD8+ T cell aging. Leptin signaling prevents p38-dependent CD8+ T cell senescence. Furthermore, plasma leptin levels are negatively related to intratumoral CD8+ T cell senescence in cancer patients. Our findings identify an unappreciated interplay between metabolic perturbation and T cell aging and suggest that modulating adipocyte-derived leptin levels may be a promising therapeutic strategy for older cancer patients. |
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