Dataset Information

Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma.

ABSTRACT: The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course.

SUBMITTER: Lee KA

PROVIDER: S-EPMC8938272 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma.

Lee Karla A KA Thomas Andrew Maltez AM Bolte Laura A LA Björk Johannes R JR de Ruijter Laura Kist LK Armanini Federica F Asnicar Francesco F Blanco-Miguez Aitor A Board Ruth R Calbet-Llopart Neus N Derosa Lisa L Dhomen Nathalie N Brooks Kelly K Harland Mark M Harries Mark M Leeming Emily R ER Lorigan Paul P Manghi Paolo P Marais Richard R Newton-Bishop Julia J Nezi Luigi L Pinto Federica F Potrony Miriam M Puig Susana S Serra-Bellver Patricio P Shaw Heather M HM Tamburini Sabrina S Valpione Sara S Vijay Amrita A Waldron Levi L Zitvogel Laurence L Zolfo Moreno M de Vries Elisabeth G E EGE Nathan Paul P Fehrmann Rudolf S N RSN Bataille Véronique V Hospers Geke A P GAP Spector Tim D TD Weersma Rinse K RK Segata Nicola N

Nature medicine 20220228 3

The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples fro ...[more]

PMID: 35228751

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Project description:Immunotherapy has led to a paradigm shift in the treatment of several cancers. There have been significant efforts to identify biomarkers that can predict response and toxicities related to immune checkpoint inhibitor (ICPI) therapy. Despite these advances, it has been challenging to tease out why a subset of patients benefit more than others or why certain patients experience immune-related adverse events (irAEs). Although the immune-modulating properties of the human gut bacterial ecosystem are yet to be fully elucidated, there has been growing interest in evaluating the role of the gut microbiome in shaping the therapeutic response to cancer immunotherapy. Considerable research efforts are currently directed to utilizing metagenomic and metabolic profiling of stool microbiota in patients on ICPI-based therapies. Dysbiosis or loss of microbial diversity has been associated with a poor treatment response to ICPIs and worse survival outcomes in cancer patients. Emerging data have shown that certain bacterial strains, such as Faecalibacterium that confer sensitivity to ICPI, also have a higher propensity to increase the risk of irAEs. Additionally, the microbiome can modulate the local immune response at the intestinal interface and influence the trafficking of bacterial peptide primed T-cells distally, influencing the toxicity patterns to ICPI. Antibiotic or diet induced alterations in composition of the microbiome can also indirectly alter the production of certain bacterial metabolites such as deoxycholate and short chain fatty acids that can influence the anti-tumor tolerogenesis. Gaining sufficient understanding of the exact mechanisms underpinning the interplay between ICPI induced anti-tumor immunity and the immune modulatory role gut microbiome can be vital in identifying potential avenues of improving outcomes to cancer immunotherapy. In the current review, we have summarized and highlighted the key emerging data supporting the role of gut microbiome in regulating response to ICPIs in cancer.

Dataset Information

Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma.

Publications

Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma.

Similar Datasets

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