Dietary fiber and probiotics impact the gut microbiome and melanoma immunotherapy response

Gut bacteria modulate response to immune checkpoint blockade (ICB) treatment in cancer, but the impact of diet and supplements on this interaction is not well-studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel pre-clinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in pre-clinical models, demonstrating impaired treatment response to anti-PD(L)-1 therapy in mice receiving a low fiber diet or probiotics, with a lower frequency of interferon-gamma-positive cytotoxic T-cells in the tumor microenvironment. Together, these data have clinical implications in patients receiving ICB for cancer. Additional resources related to software and analysis of this work is also publicly available on GitHub at https://github.com/mda-primetr/Spencer_et_al_2021.