CTLA4 and cancer: In the TME, classic Tregs, as defined by expression of CD4, CD25, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4/CD152), the Forkhead Box P3 transcription factor (32, 33), and Helios (34), directly promote immune evasion and the formation of a pro-tumorigenic TME, and prompt the growth and metastasis of various malignant tumors such as lung, ovary, breast, and prostate (35).