CTLA4 and neoplasm: In addition to the production of cytokines like VEGF and metabolic factors like adenosine, PGE2, the tumor utilizes the recruitment of TREG cells or myeloid-derived suppressor cells (MDSCs), as well as the ligation of inhibitory receptors (e.g., CTLA-4, PD-1, Tim-3) on immune effector cells to generate adaptive immune resistance.