Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review

Frontiers in Oncology

Qun Dai¹  Cuncong Zhong²  Ben Liu³  Huanbo Zhu⁴  Meizhang Li⁵  Weijing Sun⁶  Kathan Mehta⁷  Shahid Umar⁸  Chao Huang⁹  Jun Zhang⁹  Prakash Neupane⁹  Chengliang Huang⁹  Fen Wang⁹  Xianming Fan⁹ 

[1] Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China;Department of Cancer Biology, University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States;Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS, United States;;Department of Gastrointestinal Surgery, The Second Affiliated Hospital &Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States;Department of Radiation Oncology, University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States;Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China;Department of Surgery, University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, United States;Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States;

关键词: gut microbiome;    modulating factors;    immunotherapy;    solid tumors;    diet;    microbiota;   

DOI  :  10.3389/fonc.2021.642110

来源: DOAJ

【 摘 要 】

Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet.Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included.Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of “ICI-favoring” gut microbiome (P = 0.0476).Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.

【 授权许可】

Unknown