Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy

Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) proteins transformed the management of advanced cancers. Many tumor-intrinsic factors modulate immunological and clinical responses to such therapies, but ample evidence also implicates the gut microbiome in responses. The gut microbiome, comprising the bacteria, archaea, fungi, and viruses that live in the human digestive tract, is an established determinant of host immunity, but its impact on response to ICI therapy in mice and humans with cancer has only recently been appreciated. Therapeutic interventions to optimize microbiota composition to improve immunotherapy outcomes show promise in mice and humans with cancer. In this review, we discuss the rationale for gut microbiome–based cancer therapies, the results from early-phase clinical trials, and possible future developments.