CD4 and hepatocellular carcinoma: Physical conditions (e.g. overload of lactic acid, low pH, hypoxia) [67], severe “metabolic competition” with tumor cells, a lack of CD4+ T cells help (moreover, interact with Tregs and other suppressor cells) [64, 68], and high expression of a large amount of immunoregulatory molecules in T cells or HCC cells (e.g. IL-10, Fas/FasL, CXCL17, VEGF, indoleamine-2,3-dioxygenase and so on) [67, 69–71], may be responsible for restricted tumor-associated antigens (TAAs)-specific CD8+ T cell responses and poor IFN-γ production of CTLs [72, 73].