CTLA4 and cancer: During cancer progression, to counterbalance the antitumor Th1/CTLs immune response, dMMR/MSI cancer cells upregulate the expression of multiple active immune-checkpoints (ICKs) such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) causing functional exhaustion and a lack of response by tumor-infiltrating lymphocytes (TILs).