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Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer.

ABSTRACT: Accumulating evidence suggests that gut microbial dysbiosis is implicated in colorectal cancer (CRC) initiation and progression through interaction with host immune system. Given the intimate relationship between the gut microbiota and the antitumor immune responses, the microbiota has proven to be effective targets in modulating immunotherapy responses of preclinical CRC models. However, the proposed putative mechanisms of how these bacteria affect immune responses and immunotherapy efficacy remains obscure. In this review, we summarize recent findings of clinical gut microbial dysbiosis in CRC patients, the reciprocal interactions between gut microbiota and the innate and/or the adaptive immune system, as well as the effect of gut microbiota on immunotherapy response in CRC. Increased understanding of the gut microbiota-immune system interactions will benefit the rational application of microbiota to the clinical promising biomarker or therapeutic strategy as a cancer immunotherapy adjuvant.

SUBMITTER: Hou X

PROVIDER: S-EPMC9681148 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer.

Hou Xinxin X Zheng Zongmei Z Wei Jiao J Zhao Ling L

Frontiers in immunology 20221108

Accumulating evidence suggests that gut microbial dysbiosis is implicated in colorectal cancer (CRC) initiation and progression through interaction with host immune system. Given the intimate relationship between the gut microbiota and the antitumor immune responses, the microbiota has proven to be effective targets in modulating immunotherapy responses of preclinical CRC models. However, the proposed putative mechanisms of how these bacteria affect immune responses and immunotherapy efficacy re ...[more]

PMID: 36426359

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Project description:BackgroundThere have been previously reported associations between the gut microbiota, immune cells, and colorectal cancer; however, the specific mechanisms underlying these relationships remain largely unexplored and require further research. Therefore, in this study, we aimed to unravel the interactions between the gut microbiota, immune cells, and colorectal cancer.MethodsThe analysis used genome-wide association study (GWAS) data encompassing 207 microbial taxa and 205 functional pathways and data on 731 immune cell phenotypes. Colorectal cancer data on 6 581 cases and 463 421 controls were sourced from the Integrative Epidemiology Unit Open GWAS Project. Univariate inverse-variance weighted Mendelian randomization analysis was used to identify gut microbial taxa associated with colorectal cancer. Mediation analysis was used to identify the mediating role of specific immune cells in the link between gut bacteria and colorectal cancer.ResultsUnivariate inverse-variance weighted Mendelian randomization analysis revealed that several microbial taxa from the Actinobacteria and Firmicutes phyla were significantly associated with colorectal cancer. Coriobacteriaceae (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.72-0.97), Sutterellaceae (OR: 0.88, 95% CI: 0.78-0.99), Eggerthella (OR: 0.91, 95% CI: 0.84-0.99), Coriobacteriales (OR: 0.84, 95% CI: 0.72-0.97), Collinsella aerofaciens (OR: 0.85, 95% CI: 0.74-0.99), and Ruminococcus bromii (OR: 0.91, 95% CI: 0.83-0.99) were negatively associated with colorectal cancer, whereas Lactobacillales (OR: 1.11, 95% CI: 1.03-1.20), Veillonella (OR: 1.08, 95% CI: 1.01-1.15), and Bifidobacterium bifidum (OR: 1.05, 95% CI: 1.00-1.09) were positively associated with colorectal cancer. Mediation analysis revealed that in the causal pathway from Collinsella aerofaciens to colorectal cancer, CD127 on CD28+ CD45RA- CD8br and human leukocyte antigen (HLA) DR on CD33- HLA DR+, mediated 11.30% and - 6.52% of the effect, respectively, and that in the causal pathway from Ruminococcus bromii to colorectal cancer, IgD- CD38dim %lymphocyte mediated - 14.80% of the effect.ConclusionsThese results highlight the potential of gut microbiota and immune cell phenotypes as novel treatment strategies for colorectal cancer.

Dataset Information

Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer.

Publications

Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer.

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