Abstract
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.
Highlights
Immunotherapy such as using immune checkpoint inhibitors (ICIs) targeting PD-1/L1 and CTLA-4 has revolutionized our management of various cancer types including lung cancer [1, 2]
Original clinical studies in human subjects written in English, with the publishing date before Apr 1st, Abbreviations: AEs, adverse effects; ICIs, immune checkpoint inhibitors; irAEs, immune-related AEs; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; RCC, renal cell carcinoma; HCC, hepatocellular carcinoma; FMT, fecal microbiota transplantation; SCFA, short chain fatty acids
Since gut microbiome impacts cancer immunotherapy, we investigated whether diet will have effect on gut microbiome that could potentially affect cancer immunotherapy
Summary
Immunotherapy such as using immune checkpoint inhibitors (ICIs) targeting PD-1/L1 and CTLA-4 has revolutionized our management of various cancer types including lung cancer [1, 2]. The gut microbiome, due to its close interaction with immune system, has gained increasing attention for its potential role in cancer immunotherapy [4, 5]. This is supported by several preclinical models [6, 7], as well as correlative studies at the human level including ours [8]. Several key questions remain to be addressed: [1] whether there is shared feature of gut microbiome that links to ICI response and AEs across various solid tumors; [2] whether antibiotics can affect cancer immunotherapy. 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
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