Fusobacterium nucleatum, succinate signaling, and immunotherapy resistance in colorectal cancer: clinical relevance and translational opportunities.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors have changed the treatment landscape in several tumor types, their clinical benefit in CRC remains largely confined to mismatch repair-deficient disease. Most colorectal cancers are microsatellite-stable and show primary resistance to immunotherapy, highlighting the need to better understand tumor microenvironmental factors that shape immune responsiveness. Increasing evidence suggests that the tumor-associated microbiota contributes to CRC progression and treatment response. Among the implicated taxa, Fusobacterium nucleatum (Fn) is frequently enriched in colorectal tumors and is associated with adverse clinicopathologic features, poor prognosis, and reduced sensitivity to systemic therapies. Recent studies further suggest that Fn-related succinate accumulation may promote myeloid-dominated immune suppression and impaired cytotoxic T-cell activity. In this review, we summarize current evidence linking the Fn-succinate axis to immune regulation in CRC, discuss its relevance to immunotherapy resistance, and highlight key translational challenges.