Dietary fructose-mediated adipocyte metabolism drives antitumor CD8+ T cell responses

Abstract

Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8+ Tcell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltrating CD8+ Tcells reveals that dietary fructose mediates attenuated transition of CD8+ Tcells to terminal exhaustion, leading to a superior antitumor efficacy. High-fructose feeding initiates adipocyte-derived leptin production in an mTORC1-dependent manner, thereby triggering leptin-boosted antitumor CD8+ Tcell responses. Importantly, high plasma leptin levels are correlated with elevated plasma fructose concentrations and improved antitumor CD8+ Tcell responses in patients with lung cancer. Our study characterizes a critical role for dietary fructose in shaping adipocyte metabolism to prime antitumor CD8+ Tcell responses and highlights that the fructose-leptin axis may be harnessed for cancer immunotherapy.