Immunotherapy in advanced colorectal cancer: Current landscape, mechanisms, challenges, and future directions

ObjectiveTo summarize the current status, mechanisms, challenges, and future directions of immunotherapy in advanced rectal cancer.Data SourcesPublished clinical trials, translational studies, and mechanistic reports on immunotherapeutic strategies for colorectal and rectal cancer.Data SummaryImmune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 and CTLA-4 blockade, show promise in MSI-H rectal cancer, while combination therapies are under investigation for microsatellite stable (MSS) tumors. Tumor vaccines and T-cell-based approaches, such as CAR-T and TCR-engineered therapies, are emerging strategies. Major barriers include immune evasion, microenvironment heterogeneity, and resistance mechanisms in MSS disease.ConclusionsImmunotherapy is transforming the treatment landscape of advanced rectal cancer, yet challenges persist. Continued mechanistic exploration and rational combination strategies are essential to improve response rates and expand benefit to MSS patients.