CD4 and neoplasm: Among these immune cells, CD8+ T cells exert cytotoxic effects through secreting TNF, perforin, and granzymes (95), and CD4+ T cells further activate other immune cells by secreting IL-1, IL-6, IFN-γ, and other cytokines (96, 97), in which IL-1 and IL-6 play important roles to polarize macrophages toward M1 type with anti-tumor functions (98).