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Clin Transl Med. 2019 Mar 18;8(1):9. doi: 10.1186/s40169-019-0225-x.

The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies.

Author information

1
Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
2
Department of Internal Medicine, Harbor-UCLA Medical Center, 1000 W Carson St, Torrance, CA, 90509, USA.
3
Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Building 51, Room 101, 1500 E Duarte St, Duarte, CA, 91010, USA. rsalgia@coh.org.

Abstract

There is growing interest in identifying predictive biomarkers for inhibitors of programmed cell death protein 1 receptor (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). Given the links between the stool microbiota, anticancer immunosurveillance, and general health, the composition of the gut microbiome has recently undergone investigation as a biomarker for immunotherapy. In this review, we highlight published results from preclinical and clinical studies to date supporting a relationship between the gut microbiome and antitumor efficacy of immune checkpoint inhibitors. Despite the promising and hypothesis-generating findings that have been produced in this arena to date, there remain some inconsistencies amongst present data that may need to be resolved to contribute to further development. Among these, a better understanding of the immunomodulatory function of the microbiome, standardization in sampling, sequencing techniques, and data analysis, and ensuring uniformity across various aspects of study design are warranted in conducting future prospective studies seeking to validate the gut microbiome as a potential biomarker of response to checkpoint blockade.

KEYWORDS:

Biomarkers; CTLA-4; Commensal bacteria; Gut microbiome; Immune checkpoint inhibitors; PD-1; PD-L1

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