Emerging evidence of immunotherapy for colorectal cancer

Since the advent of immune checkpoint inhibitors, which modulate the interplay between the tumor cell and immune system, immunotherapy has become widely recognized as a new standard treatment for cancers including microsatellite instability-high (MSI-H) colorectal cancer. Immune checkpoint inhibitors such as pembrolizumab and nivolumab (anti-PD-1 antibodies) that act in the effector phase of T cells and ipilimumab (anti-CTLA-4 antibody) that acts mainly in the priming phase are now in clinical use. These antibodies have shown therapeutic efficacy in MSI colorectal cancer patients who have failed to respond to existing standard therapies. Pembrolizumab is also strongly recommended as first-line therapy for MSI-H metastatic colorectal cancer. Therefore, the MSI status and tumor mutation burden of the tumor should be clarified before starting treatment. Because many patients do not respond to immune checkpoint inhibitors, combination therapies with immune checkpoint inhibitors, including chemotherapy, radiotherapy, or molecularly targeted agents, are being investigated. Furthermore, treatment methods for preoperative adjuvant therapy for rectal cancer are being developed.