Matson et al. analyzed stool samples from metastatic melanoma patients prior to anti-PD-1 treatment and found that the species composition of the commensal microbiota was significantly associated with clinical efficacy, with the ratio of beneficial to non-beneficial bacteria being a strong predictor of response. Germ-free mice reconstituted with human fecal matter from responders or non-responders led to the correspondingly enhanced or diminished tumor control, T cell response, and efficacy with anti-PD-L1 therapy in 2 of 3 mice in each group.
Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.
Author Info: (1) Department of Pathology, University of Chicago, Chicago, IL 60637, USA. (2) Department of Pathology, University of Chicago, Chicago, IL 60637, USA. (3) Center for Research Info
Author Info: (1) Department of Pathology, University of Chicago, Chicago, IL 60637, USA. (2) Department of Pathology, University of Chicago, Chicago, IL 60637, USA. (3) Center for Research Informatics, University of Chicago, IL 60637, USA. Department of Pediatrics, University of Chicago, IL 60637, USA. (4) Department of Medicine, University of Chicago, Chicago, IL 60637, USA. (5) Department of Medicine, University of Chicago, Chicago, IL 60637, USA. (6) Department of Medicine, University of Chicago, Chicago, IL 60637, USA. (7) Department of Medicine, University of Chicago, Chicago, IL 60637, USA. (8) Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
