Meanwhile, the exhaustion of infiltrated CTLs can be induced by the immune suppressive checkpoints in TME, e.g., the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) or the cytotoxic T lymphocyte antigen-4 (CTLA-4), which hindered the development of anti-tumor specific CTLs responses (62). Here, CTLA4 is linked to neoplasm.