Immune Checkpoint Blockade Therapies for Colorectal Cancer: Current Strategies and Emerging Approaches

There have been significant advances in colorectal cancer (CRC) immunotherapy over the past decade, with incorporation into both the metastatic and adjuvant/neoadjuvant treatment spaces. However, there remains a large unmet need in the CRC population, with a minority of cancers currently addressable with existing immunotherapeutic solutions. This review summarizes both our current approach and the novel therapeutics, which may soon be a part of standard practice. Current treatments focus on targeting inhibiting PD-1 and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) pathways with antibodies, such as pembrolizumab, nivolumab, and ipilimumab. Meanwhile, there are numerous novel immunotherapeutic approaches being investigated. Recent studies have shown that Fc-enhanced PD-1/CTLA-4 antibodies can have an impact in microsatellite stable CRC. Other work has evaluated new combinatorial pathways with classic PD-1 blockade to expand response, such as LAG-3, TIGIT, and NKG2A. These treatments have been used in trials for use in metastatic CRC and in possible novel adjuvant/neoadjuvant therapies. Additional immune checkpoint inhibitor options may be incorporated into CRC trials in the near future as regimens targeting TIM-3, OX40, CD137, and VISTA, among others, have been recently investigated in advanced solid tumor trials. These approaches suggest a bright future for CRC immunotherapy with an expansion of effective immunotherapeutic options available for patients with CRC, leading to improved outcomes and quality of life.