CTLA4 and neoplasm: Aggregation and growth of tumor cells formed an immune impressive tumor microenvironment (TME), which is low oxygen, low pH, high metabolic waste, high immune-suppressive cytokines, and the upregulation of immune-checkpoint, such as PD-L1 and CTLA-4; those factor made the immune cells can hardly recognize and lyse the cancer cell [4, 5].