Invisible influencers: the tumor microbiome’s impact on immunotherapy in colorectal cancer (CRC)

INTRODUCTION: The tumor microbiome, a diverse microbial community within the tumor microenvironment (TME), significantly influences cancer progression and immunotherapy outcomes in colorectal cancer (CRC). Understanding its role in modulating immune responses and therapeutic resistance is critical for advancing precision oncology. AREAS COVERED: This review examines the tumor microbiome's impact on CRC immunotherapy, focusing on immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 and anti-CTLA-4. It explores microbial composition, their immune-modulatory mechanisms, and metabolite-driven resistance pathways, including short-chain fatty acids and polyamines. Emerging strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and targeted antibiotics are discussed, alongside challenges in personalizing microbiome-based therapies. Literature was sourced from peer-reviewed studies on tumor microbiome dynamics and immunotherapy resistance. EXPERT OPINION: The tumor microbiome shapes CRC immunotherapy efficacy by modulating immune evasion and TME dynamics. Targeted interventions like FMT and probiotics show promise in enhancing ICI responses, but challenges include microbial variability, safety concerns, and ethical considerations. Future research should prioritize personalized microbiome profiling and standardized protocols to optimize therapeutic outcomes and overcome resistance in CRC.

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