Advances in immune checkpoint inhibitor therapy for microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) colorectal cancer: Insights from the tumor immune microenvironment

This review systematically analyzes the relationship between the immune microenvironment characteristics of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) colorectal cancer (CRC) and the efficacy of immune checkpoint inhibitors (ICIs). The article emphasizes that this tumor subtype has a high mutation burden, abundant neoantigens, and significant immune cell infiltration, explaining its high sensitivity to immunotherapy, while also pointing out that some patients exhibit primary non-response or subsequent resistance. Based on single-cell and spatial omics, as well as multi-omics integration analyses, the authors reveal the complexity and heterogeneity of key immune cell subpopulations, spatial distribution, and resistance mechanisms (such as abnormal Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways, human leukocyte antigen (HLA) loss, and metabolic reprogramming, and propose the necessity of multi-time-point dynamic monitoring and multimodal combination therapy. The study underscores that, in the future, standardized data integration and the establishment of artificial intelligence (AI) prediction models will be required to facilitate the implementation of precise, individualized immunotherapy strategies, thereby further improving clinical efficacy.