Colorectal cancers (CRCs) have been identified as potential targets for 
immunotherapy with programmed cell death (PD)-1 inhibitors. English-language 
publications from MedLine and Embase that evaluated PD-1/PD ligand 1 (PD-L1) in 
the CRC tumor microenvironment and clinical trials that assessed PD-1 inhibitors 
were included. Sixteen abstracts were screened. Fifteen met the inclusion 
criteria. After review of the full texts, this resulted in a final reference 
list of 8 studies eligible for review. Five studies that assessed PD-1/PD-L1 in 
CRC and 3 trials that assessed PD-1 inhibitors were included. PD-1-positive 
(PD-1+) tumor-infiltrating lymphocytes and PD-L1+ cancer cells featured more 
prominently in high-level microsatellite instability (MSI-H) CRCs compared with 
microsatellite stable (MSS) CRCs, except in 1 study in which PD-L1 expression 
was higher in MSS CRCs. In the 3 trials that assessed PD-1 inhibitor, all 3 
studies recruited patients with metastatic CRC (mCRC). One study also included 
patients with recurrent CRC. The objective response according to the Response 
Evaluation Criteria in Solid Tumors criteria was 0% (19 CRC patients with 
unknown microsatellite instability status) in the nivolumab study. In the 
pembrolizumab study, the objective response to PD-1 inhibitor was 40% and 0% in 
patients with MSI-H and MSS mCRC, respectively (10 patients in the MSI-H group, 
18 patients in the MSS group). Seventy-eight percent of the patients in the 
MSI-H mCRC group compared with 11% in the MSS mCRC group (P < .005) showed no 
further disease progression at 12 weeks. In the nivolumab with or without 
ipilimumab study, objective partial response at 12 weeks to PD-1 inhibitor with 
or without cytotoxic T-lymphocyte-associated protein 4 inhibitor was 25.5% to 
33.3% and 5% in the MSI-H and MSS groups, respectively (100 patients in the 
MSI-H group, 20 patients in the MSS group). Clinical trials that assessed PD-1 
inhibitor immunotherapy in patients with CRC have recruited only small cohorts 
of patients with mCRC. Studies on the tumor microenvironment have been on the 
basis of archival specimens with different antibody PD-1 and PD-L1 preparations 
for immunohistochemistry, independent from immunotherapy trials. Immunotherapy 
with PD-1 therapy has potential benefit for immunogenic MSI-H CRCs whereas there 
is no evidence to date to suggest immunotherapy benefit in MSS CRCs. The 
available data are limited, and there is no information on non-mCRCs. Future 
trials are under way to determine its benefits.