Thomas J, et al. - In the present study, the researchers sought to describe the development and decision-making of immune checkpoints (ICIs) in the treatment of deficiency in mismatch repair (dMMR) colorectal cancer (CRC) and to address ongoing clinical trials in this therapeutic space. ICIs targeting the PD1/PDL1 axis and CTLA-4 were examined and show robust clinical results with prolonged progression-free survival in non-randomized single arm clinical trials. Based on these results, the FDA approved single-agent therapy with pembrolizumab and nivolumab and combination therapy with nivolumab/ipilimumab for metastatic CRC that progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Ongoing clinical trials evaluate the use of these agents in earlier treatment lines like metastatic frontline therapy and adjuvant therapy for stage III CRC. Resistance to ICIs does, however, exist in a subset of patients and ongoing clinical trials are exploring new strategies in these refractory patients with PD-1.