Science (2 November 2017) doi:10.1126/science.aan4236 & doi:10.1126/science.aan3706

Immunotherapy that uses checkpoint blockade via inhibitors can provide clinical benefit to some but not all patients with cancer. In Science, two reports describe the influence of the patient’s gut microbiome on the response to checkpoint inhibition with antibody to the immunoinhibitory receptor PD-1 (anti-PD-1). Gopalakrishnan et al. report that patients with melanoma who respond to anti-PD-1 have greater diversity in their gut microbiota—particularly more Clostridiales and Ruminococcaceae but less Bacteroidales—than do non-responding patients. Routy et al. show that patients with epithelial tumors who are treated with antibiotics respond less well to anti-PD-1 immunotherapy. Both studies show that the transfer of fecal microbiota to germ-free or antibiotic-treated tumor-bearing mice influences the response to checkpoint inhibitor blockade. In particular, Routy et al. show that monocolonization with Akkermansia muciniphila confers a protective anti-tumor response by inducing expression of the cytokine IL-12 and promoting the infiltration of effector T cells in tumors. These findings suggest a role for the gut microbiome in patients’ immune responses to tumors. LAD