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28-01-2019 | Immunotherapy | At a glance | Article

Gut microbiota and immunotherapy response: A round-up of the trials

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

 ---

Gopalakrishnan et al [2]

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

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

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