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Available4.9
14 reviewsSUMMARYT cell dysfunction with age underlies an increased incidence of cancer in elderly individuals; however, howT cell aging is triggered in the tumor microenvironment is unclear. Here, we show that an age-associatedreduction 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 intratumoralsenescent CD8+ T cells increases with age, leading to a weak antitumor effect. Moreover, decreased levelsof 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 intratumoralCD8+ 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 apromising therapeutic strategy for older cancer patients.
4.5
16 reviews