Several immune cells inhibit the function of effector T-cells to dampen the efficacy of ICIs through direct contact, releasing suppressive molecules (TGF-β and IL-10) and upregulation of immune checkpoints (PD-1, CTLA-4, TIM-3, and LAG-3), including T regulatory cell (Treg), B regulatory cell (Breg), M2 Tumor-associated macrophages (TAMs), and Myeloid-derived-suppressor cells (MDSC) [53]. This evidence concerns the gene CTLA4 and neoplasm.