Microbiota and immune-related adverse events in cancer immunotherapy

In response to treatment with immune checkpoint inhibitors (ICIs), patients with cancer can develop immune-related adverse events (irAEs), which are off-target toxicities affecting non-tumour tissues. Development of an irAE can require cessation of ICI treatment and cause additional morbidities, unrelated to cancer. Although the mechanisms that drive irAEs remain largely unknown, thus limiting treatment strategies, emerging evidence implicates tissue microbiomes, particularly in the gastrointestinal tract, lung and skin, as potential mediators. Here we review evidence that supports roles for the microbiome in irAEs. We focus on ICI colitis, a common irAE that has strong association with the gut microbiome. We examine clinical and preclinical studies that shed light on the immune and microbial drivers of ICI colitis and discuss current experimental treatments. By summarizing recent findings, we aim to encourage research into therapies that reduce irAE risk and severity while preserving anti-tumour efficacy of ICI treatment.