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

Abdul Rafeh Naqash; Alba J Kihn-Alarcón; Chara Stavraka; Kathleen Kerrigan; Saman Maleki Vareki; David James Pinato; Sonam Puri

doi:10.21037/atm-20-6427

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

Ann Transl Med. 2021 Jun;9(12):1034. doi: 10.21037/atm-20-6427.

Authors

Abdul Rafeh Naqash¹, Alba J Kihn-Alarcón², Chara Stavraka³, Kathleen Kerrigan⁴, Saman Maleki Vareki^{5

6

7}, David James Pinato⁸, Sonam Puri⁴

Affiliations

¹ Department of Investigational Cancer Therapeutics, National Cancer Institute, Bethesda, MD, USA.
² Department of Research, Liga Nacional Contra el Cáncer & Instituto de Cancerología, Guatemala City, Guatemala.
³ Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK.
⁴ Division of Medical Oncology Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA.
⁵ Division of Experimental Oncology, Department of Oncology, University of Western Ontario, London, ON, Canada.
⁶ Department of Pathology and Laboratory Medicine, University of Western Ontario, London, ON, Canada.
⁷ Cancer Research Laboratory Program, Lawson Health Research Institute, London, ON, Canada.
⁸ Department of Surgery and Cancer, Imperial College, London, UK.

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.

Keywords: Gut microbiome; immunotherapy; response; toxicity.

Publication types

Review