The gut microbiome has emerged as an unlikely influencer of response to treatment with immune checkpoint inhibitors across various tumor types. Here we provide a brief summary of the key studies – all published in Science – that have investigated this association.
The two earlier studies in mice and the three recent ones involving patients all showed that the constitution of the gut microbiome is a crucial factor in determining the efficacy of immunotherapeutic agents, with specific bacterial species shown to have a role.
In addition, two of the three studies in humans found that the microbiota diversity was higher among patients who responded to immunotherapy than those who did not. Finally, all three studies showed that fecal transfer from responding and nonresponding patients to various mouse models of cancer mimicked the patient phenotype in the animals.
Read on for details of the main findings from these studies.
Key findings from the studies in patients
Publication details | Tumor type/s | Immunotherapy type | Bacterial species enriched in responders | Bacterial species enriched in nonresponders |
Routy et al [1] | Advanced NSCLC or RCC | Anti-PD-1/PD-L1 | Firmicutes; Akkermansia muciniphila | --- |
Metastatic melanoma | Anti-PD-1 | Clostridiales order; Ruminococcaceae family; Faecalibacterium genus | Bacteroidales order, including Bacteroides thetaiotaomicron and Anaerotruncus colihominis; Escherichia coli | |
Matson et al [3] | Metastatic melanoma | Anti-PD-1 mainly, but anti-CTLA-4 in four patients | Enterococcus faecium; Collinsella aerofaciens; Bifidobacterium adolescentis; Klebsiella pneumoniae; Veillonella parvula; Parabacteroides merdae; Lactobacillus spp.; Bifidobacterium longum | Ruminococcus obeum, Roseburia intestinalis |
Abbreviations: CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; NSCLC, non-small-cell lung cancer; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; RCC, renal cell carcinoma
Key findings from the studies in mouse models
Publication details | Tumor type/s | Immunotherapy type | Bacterial species associated with efficacy |
Vétizou et al [4] | Sarcoma, melanoma, and colon cancer | Anti-CTLA-4 | Bacteroides spp., including Bacteroides fragilis and Bacteroides thetaiotaomicron; Burkholderia cepacia |
Sivan et al [5] | Melanoma | Anti-PD-L1 | Bifidobacterium spp. |
Abbreviations: CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; NSCLC, non-small-cell lung cancer; PD-L1, programmed cell death ligand 1; RCC, renal cell carcinoma
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