Commensal microbiota associated with anti-PD-1 efficacy in metastatic melanoma patients. microbiome

Anti-PD-1-based immunotherapy is having a major impact on cancer outcomes but only benefits a subset of patients. Among the variables that could contribute to inter-patient heterogeneity is differential composition of the commensal microbiota, which preclinically has been shown to affect anti-tumor immunity and immunotherapy efficacy in mice. Baseline stool samples were analyzed from metastatic melanoma patients prior to immunotherapy treatment, through an integration of 16S rRNA sequencing, metagenomic shotgun sequencing, and quantitative PCR for selected bacteria. A significant association between commensal microbial composition and clinical response was observed. Reconstitution of germ-free mice with fecal material from a responding patient led to improved tumor control, augmented T cell responses, and a distinct microbiota compared to a non-responding patient. Our results indicate a mechanistic impact of the commensal microbiota on anti-tumor immunity in human cancer patients.