For instance, cholangiocarcinoma (CCA) cells with positive PD-1 and CTLA-4, have been reported to form immunosuppressive TME by decreasing the amount of cytotoxic immune cells, increasing the amount of Tregs and making tumor-infiltrating T cells to express receptors of PD-1 and CTLA-4. Here, CTLA4 is linked to cholangiocarcinoma.