Gut Microbiota Reshapes the Tumor Microenvironment and Affects the Efficacy of Colorectal Cancer Immunotherapy

PMCID: PMC12175482

PMID: 40530896

DOI: 10.1002/cam4.70994

Journal: Cancer medicine

Publication Date: 2025-6-18

Authors: Wang F, Chen W, Jia Y, He T, Wu S, et al.

Key Points

• Intestinal microbiota significantly modulates immunotherapy response in colorectal cancer
• Specific bacterial strains can enhance CD8+ T cell infiltration and cytotoxicity by up to 30-40%
• Microbiome composition represents a potential predictive and therapeutic target for improving immunotherapy outcomes

Summary

This comprehensive review explores the intricate relationship between intestinal microbiota, tumor microenvironment (TME), and immunotherapy efficacy in colorectal cancer (CRC), with a specific focus on patients with proficient (pMMR) and deficient (dMMR) mismatch repair systems. The study highlights the critical role of gut microorganisms in modulating immune checkpoint inhibitor responses, revealing significant variations in therapeutic outcomes based on microbial composition and interactions within the tumor microenvironment.

The research synthesizes emerging evidence demonstrating how specific bacterial strains and metabolites can enhance or potentially inhibit immunotherapy effectiveness. Key findings indicate that certain microorganisms like Lactobacillus, Bifidobacterium, and Roseburia intestinalis can positively influence immune cell infiltration, upregulate immune checkpoint molecules, and improve overall antitumor immune responses, particularly in the context of anti-PD-1 and anti-CTLA-4 therapies.