Role of the Gut-brain Axis in the Cancer-immunity Cycle

Antitumor immunity depends on a self-reinforcing cancer-immunity cycle, yet many tumors evade critical steps and respond poorly to checkpoint blockade. Emerging evidence indicates that gut microbiota-derived systemic cues could influence these therapeutic outcomes, highlighting the gut-brain axis (GBA) as a potentially important regulatory framework in cancer immunity. In this review, we summarize how GBA-related signals may influence multiple stages of the cycle through interconnected neural, endocrine, microbial, and immune pathways. Current findings suggest that these impacts are highly context-dependent, and some microbiota-associated findings may reflect direct microbiota-immune crosstalk rather than strictly defined GBA-mediated regulation. Since most mechanistic evidence remains preclinical and superficial, cautious interpretation is required. Integrated multiomics approaches may help to clarify regulatory networks, support biomarker discovery, and inform patient stratification for future precision cancer immunotherapy.