Sucralose Consumption Ablates Cancer Immunotherapy Response through Microbiome Disruption
Menée à l'aide de lignées cellulaires, de modèles murins et de données concernant les antécédents alimentaires de patients atteints d'un cancer de stade avancé traité par anti-PD-1, cette étude met en évidence un mécanisme par lequel la consommation de sucralose, un édulcorant artificiel, inhibe la réponse des cellules cancéreuses à l'immunothérapie en perturbant le microbiome
Gut microbiota composition is directly associated with response to immunotherapies in cancer. The impact of diet on the gut microbiota and downstream immune responses to cancer remains unclear. In this study, we show that consumption of a common nonnutritive sweetener, sucralose, modifies microbiome composition, restricts T-cell metabolism and function, and limits immunotherapy response in preclinical models of cancer and patients with advanced cancer treated with anti–PD-1–based immune checkpoint inhibitors. Sucralose consumption is associated with a reduction in microbiota-accessible arginine, and amino acid supplementation or fecal microbiome transfer from anti–PD-1 responder mice completely restores T-cell function and immunotherapy response. Overall, sucralose consumption destabilizes the gut microbiota, resulting in compromised T-cell function and ablated immune checkpoint inhibitor response in cancer.
Cancer Discovery , résumé, 2025