In vitro exposure to sucralose ablates CD8 T cell responses

The composition of the gut microbiota is directly associated with response to checkpoint inhibitors in cancer. How diet impacts the gut microbiota and downstream immune response to cancer remains unclear. Here, we show that consumption of a common artificial sweetener, sucralose, supports microbial dysbiosis, restricts T cell metabolism and function, and limits immunotherapy response in cancer. Microbial dysbiosis is associated with a reduction in Arginine, and amino acid supplementation or fecal microbiome transfer completely restores T cell function and immunotherapy response. Thus, artificial sweetener consumption destabilizes the gut microbiota, resulting in compromised T cell function and ablated immunotherapy response in cancer. Overall design: Gene expression analysis of bulk RNA-seq of Ot-I T cells from 3 separate mice expanded with or without Sucralose during various timecourses for 7 days