The Application and Limitations of Immunotherapy for Colorectal Cancer

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, driven by its molecular heterogeneity and resistance to conventional therapies. While surgery, chemotherapy, and radiotherapy form the backbone of CRC management, their efficacy diminishes in advanced disease, necessitating innovative approaches. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a transformative strategy, achieving remarkable success in microsatellite instability-high (MSI-H) CRC due to its high tumor mutational burden. However, microsatellite stable (MSS) CRC, comprising the majority of cases, exhibits limited responsiveness, posing a significant challenge. This review elucidates the epidemiological and pathological features of CRC, evaluates the limitations of traditional treatments, and explores the evolution and mechanisms of immunotherapy. It highlights the progress of ICIs, tumor vaccines, and cell therapies in CRC, with a focus on clinical trial outcomes demonstrating durable responses in MSI-H cohorts but modest benefits in MSS tumors. Key challenges, including biomarker identification, the immunosuppressive tumor microenvironment, and drug resistance, are analyzed, alongside strategies to overcome them. Future directions emphasize personalized therapies, tumor microenvironment modulation, and technological innovations like neoantigen vaccines and microbiome-based interventions. By synthesizing current evidence and identifying research gaps, this paper underscores immunotherapys potential to revolutionize CRC treatment while addressing its limitations, paving the way for precision oncology advancements.