The Effect of Dietary Fiber Compositions on the Therapeutic Outcome of Combined Radio- and Immunotherapy in a Preclinical Cancer Model.

Abstract

Several studies demonstrated curative responses of combined radio-immunotherapy, although not standard-of-care for most cancers. Increased fiber intake has been associated with improved radiotherapy and immunotherapy outcomes, but fiber compositions' impact remains unclear. This study aimed to explore whether dietary fiber composition influences the therapeutic outcome of combined radio-immunotherapy in a preclinical cancer model. A syngeneic mouse model of colon cancer (CT26) (female BALB/cOla Hsd) was used. Mice were randomized into three groups (n = 12) of iso-caloric diets with different fiber compositions. Five instances of local radiotherapy on tumors, combined with injections of anti-PD-L1, were administered over 5 and 10 days. Diets' impact was assessed on progression-free survival, SCFA levels in fecal and cecal samples, gut microbiome composition, and immunological profile. Progression-free survival was different between compositions, as well as their gut microbiota community structure, at all measured time-points. Therapeutic outcome (cure) was negatively associated with the relative abundance of Bacteroides and positively with Atopobiaceae Family. There was no association with SCFA levels. Cured mice displayed smaller spleens containing increased proportions of CD8+ T-cells and decreased proportions of myeloid-derived suppressor cells. Our data suggest that fiber composition may influence therapeutic outcome of combined radio-immunotherapy treatment in vivo.