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

By Vyara Matson, Jessica Fessler, R. Bao, Tara Chongsuwat, Y. Zha, M. Alegre, J. Luke, T. Gajewski. Science, 2018

2,669 citations recorded by the source corpus.

Good bacteria help fight cancer 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 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.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/f8bbf5a6d9f97ca5ad8d89a9fab3b898dd992bae

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In Molecular Biology

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Citations in the corpus

• Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors (2018, background): “Lactobacillus sp. B. longum Bifidobacterium Increased IFN-γ production and major histocompatibility complex Class IIhi DC Effective anti-tumor response Mouse [87] Faecalibacterium Increased peripheral effector CD4+ and CD8+ T cell Effective anti-tumor response Mouse/Human [88] Bacteroidales Increase”
• Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy. (2020, background): “However, manipulation of diets ultimately modulates the gut microbiome which in turn affects tumor and immune metabolism and can even play a significant role in modulating tumor responses to immunotherapy across multiple cancer types (Gopalakrishnan et al., 2018; Matson et al., 2018; Routy et al., 2”
• The microbiome and human cancer (2021, background): “thatmediates Toll-like receptor 4 (TLR4)– and IL-12–dependent TH1 responses and therapeutic efficacy (70); (iii) inhibition of programmed cell death protein 1 and/or its ligand [PD-(L)1] leads to T cell priming against melanoma and is more effective when hosts harbor Bifidobacteria species in their ”
• The microbiome and cancer (2018, background): “Two different studies of melanoma performed in the USA [91,92] revealed a variety of changes in different organisms and genera associated with response and non-response to PD-1 inhibition.”