Moreover, in the NICHE trial, which was the first neoadjuvant immunotherapy trial for CRC, 27% (4/15) of the pMMR tumors showed pathological response to ipilimumab and nivolumab, and the degree of CD8 + PD-1+ T cell infiltration was significantly higher in among the responders than in the non-responders in the pMMR group, indicating that microenvironment might be the underlying mechanism for MSS CRC benefiting from ICIs [30]. This evidence concerns the gene PDCD1 and colorectal carcinoma.