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The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer

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Title: The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer
Authors: Naqash, AR
Kihn-Alarcon, AJ
Stavraka, C
Kerrigan, K
Vareki, SM
Pinato, DJ
Puri, S
Item Type: Journal Article
Abstract: 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.
Issue Date: 1-Jun-2021
Date of Acceptance: 12-Jan-2021
URI: http://hdl.handle.net/10044/1/91631
DOI: 10.21037/atm-20-6427
ISSN: 2305-5839
Publisher: AME Publishing
Start Page: 1
End Page: 11
Journal / Book Title: Annals of Translational Medicine
Volume: 9
Issue: 12
Copyright Statement: © Annals of Translational Medicine. All rights reserved. This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Medicine, Research & Experimental
Research & Experimental Medicine
Gut microbiome
response
toxicity
immunotherapy
ANTIBIOTICS
EFFICACY
INNATE
Gut microbiome
immunotherapy
response
toxicity
Science & Technology
Life Sciences & Biomedicine
Oncology
Medicine, Research & Experimental
Research & Experimental Medicine
Gut microbiome
response
toxicity
immunotherapy
ANTIBIOTICS
EFFICACY
INNATE
Publication Status: Published
Open Access location: https://atm.amegroups.com/article/view/63735/pdf
Article Number: ARTN 1034
Online Publication Date: 2021-06
Appears in Collections:Department of Surgery and Cancer



This item is licensed under a Creative Commons License Creative Commons