CD4 and neoplasm: Such factors include, downregulation of MHC molecules and tumor antigens, development of a suppressive microenvironment by upregulation of anti-inflammatory cytokines and accumulation of immuno-suppressive cells (such as cancer-associated fibroblasts, regulatory T cell subset among the CD4+ T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and tumor-associated neutrophils), and tumor-induced immune senescence that prevents the antitumor activities of the cytotoxic cells [107].