Regulation of PD-1PD-L1 Immune Checkpoints by Gut Microbiota Metabolites and Their Clinical Translational Research: A

Xuanyou Fang1, Shuai Yuan1, Weijian Mai1

  • 1Xiaolan Clinical Institute of Shantou University Medical College, Zhongshan, Guangdong Province, China.

Abstract

Insights

Gut microbiota metabolites like SCFAs, tryptophan metabolites, and bile acids significantly impact cancer immunotherapy by modulating the PD-1/PD-L1 axis. These metabolites offer potential as biomarkers and therapeutic targets to improve treatment efficacy.

Area of Science:

  • Immunology
  • Microbiome Research
  • Cancer Therapy

Background:

  • Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have transformed cancer treatment.
  • However, variable response rates and immune-related adverse events limit their clinical utility.

Purpose of the Study:

  • To systematically review how gut microbiota metabolites influence the PD-1/PD-L1 axis.
  • To analyze molecular mechanisms of short-chain fatty acids (SCFAs), tryptophan metabolites, and bile acids in cancer immunotherapy.

Main Methods:

  • Comprehensive literature search of preclinical and clinical studies over the last decade.
  • Focus on metabolite-immune interactions, biomarker validation, and combination therapy strategies.

Main Results:

  • Gut microbiota metabolites significantly impact the tumor microenvironment and T-cell functions.
  • These metabolites influence immune tolerance and affect responsiveness to ICIs.
  • Evidence supports their role in enhancing anti-tumor immunity.

Conclusions:

  • Microbiota metabolites show promise as predictive biomarkers for ICI therapy.
  • Probiotic, fecal microbiota transplantation, and metabolite-based therapies are under investigation.
  • Further research is needed to address variability and mechanistic gaps for clinical integration.

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