Journal Article

The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients

Matson, Vyara, Luke, Jason J., Alegre, Maria-Luisa, Gajewski, Thomas F., Fessler, Jessica, Zha, Yuanyuan, Chongsuwat, Tara, Bao, Riyue

2018

Overview

Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32 Gut bacteria influence patient response to cancer therapy. 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 16 S 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.

• Publisher: The American Association for the Advancement of Science
• Subject: Animal models / Animals / Antibiotics / Antibodies, Monoclonal - therapeutic use / Anticancer properties / Antitumor activity / Bacteria / Bifidobacterium longum - classification / Bifidobacterium longum - genetics / Bifidobacterium longum - immunology / Bifidobacterium longum - isolation & purification / Cancer / Cancer immunotherapy / Dietary supplements / Effectiveness / Enterococcus faecium - classification / Enterococcus faecium - genetics / Enterococcus faecium - immunology / Enterococcus faecium - isolation & purification / Feces - microbiology / Feedback (Response) / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - immunology / Gene sequencing / Germfree / Heterogeneity / Humans / Immunity / Immunotherapy / Immunotherapy - methods / Intestinal microflora / Kidney cancer / Kidneys / Lungs / Lymphocytes T / Melanoma / Melanoma - immunology / Melanoma - therapy / Metastases / Metastasis / Mice / Microbiomes / Microorganisms / Patients / PD-1 protein / PD-L1 protein / Polymerase chain reaction / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Ribonucleic acid / RNA / RNA, Ribosomal, 16S - genetics / rRNA 16S / Skin Neoplasms - immunology / Skin Neoplasms - therapy / T-Lymphocytes - immunology