The primary mechanisms through which Tregs mediate immune suppression in the tumor microenvironment include the following: First, Tregs upregulate immune checkpoint receptors, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), thereby inhibiting the interaction between CD80 and CD86 on antigen-presenting cells and the co-stimulatory receptor CD28 on effector T cells. This evidence concerns the gene CD28 and neoplasm.