CSCs-activated TAMs also inhibit T-cell cytotoxicity by overexpressing cancer immune checkpoint receptors such as programmed death ligand protein1 (PD-L1), and (CD80/CD86)  that  interact with programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) on the surface of CD8+T cells respectively, impairing the immune response and support anti-tumor immune resistance [157–159]. This evidence concerns the gene CTLA4 and cancer.