Immune checkpoint inhibitor therapy in neoadjuvant and adjuvant treatment for cancer: A paradigm shift in the treatment of resectable gastrointestinal cancer 3)A paradigm shift in the treatment of colorectal cancer.

Immune checkpoint inhibitors, such as anti-programmed cell death-1, programmed cell death ligand-1, and cytotoxic T-lymphocyte antigen-4 monoclonal antibodies, have been notably effective in various types of cancers. Mismatch repair deficiency and microsatellite instability-high tumors have been established as striking biomarkers for response to immune checkpoint inhibitors. These biomarkers show a higher mutational burden, have cancer-associated neoantigens, and dense immune cell infiltration, which generates a robust immune response. For metastatic colorectal cancer, pembrolizumab and nivolumab, with or without ipilimumab, are recommended for chemotherapy-refractory patients, and pembrolizumab is recommended for chemotherapy-naive patients with mismatch repair deficiency and microsatellite instability-high tumors. Conversely, patients with mismatch repair-proficient and microsatellite-stable metastatic colorectal cancer showed no clinical benefit from immune checkpoint inhibitor monotherapy. Currently, combination therapy with anti-programmed cell death-1/programmed cell death ligand-1 and cytotoxic T-lymphocyte antigen-4 monoclonal antibodies or a combination of immune checkpoint inhibitors with molecular targeting agents or radiotherapy have been investigated to modulate immune cells and enhance therapeutic efficacy in mismatch repair-proficient and microsatellite-stable metastatic colorectal cancer. Furthermore, immune checkpoint inhibitors have been developed for neoadjuvant and adjuvant settings. In this review, we summarize the existing clinical data and discuss future perspectives with a focus on immune checkpoint inhibitor-based treatments for colorectal cancer.