CD4 and neoplasm: Tumor-associated antigen (TAA)-specific response and IFN-γ production by CTLs are restricted due to hypoxia, metabolic competition with cancer cells (HCCs), a deficiency in CD4+ T cells (CD4+ T cells are lacking), and the high expression of several regulatory molecules (VEGF, CXCL17, IDO, and IL-10) in the tumor microenvironment [16].