CD274 and colorectal carcinoma: One example is the MSI in CRC, where an “extrinsic” immune cell-mediated PD-L1 upregulation mechanism has been hypothesized to be exerted by the induction of an active immune microenvironment by this instability on two fronts: an immune-stimulatory effect by increased cytotoxic effector T lymphocytes on one side, and immune inhibitory effect that includes PD-1/PD-L1 checkpoint on the other [38,44,50].