Immune checkpoint inhibitors in dMMR-MSI-H colorectal cancer: rationale, progress and prospects.

Colorectal cancer (CRC) with a deficient mismatch repair and high microsatellite instability (dMMR-MSI-H) phenotype represents a biologically distinct subtype characterized by elevated tumor mutational burden and strong immunogenicity. These features contribute to their exceptional responsiveness to immune checkpoint inhibitors (ICIs), especially those targeting the PD-1 and CTLA-4 pathways. Although dMMR-MSI-H tumors constitute only a small fraction of CRC cases, their response to ICIs has redefined therapeutic standards. In this review, we discuss the immunological underpinnings that render these tumors susceptible to immune modulation, summarize key clinical trial findings, and analyze emerging resistance mechanisms.

Furthermore, we highlight the evolving landscape of predictive biomarkers and ongoing efforts to increase treatment efficacy through combination strategies and biomarker-driven approaches.