1.1 T cells are the key to the occurrence and development of tumor immune response
T cells derived from lymphoid stem cells in bone marrow and undergo differentiation and maturation in the thymus, and then distributed to immune organs and tissues throughout the body through lymphatic and blood circulation. T cells mediate cellular immunity and coordinate the whole immune response [14-15]. CD4+ or CD8+ T cells are the two most important types of T cells [16-17] studied in the development of adaptive immunity. The most important feature of adaptive immunity is characterized by specificity via stimulation of specific antigens from tumor or pathogens. The CD4+naive T cells (CD4+ Tn) can develop and differentiate into CD4+ T cells under stimulation by antigens presented by DCs. Of them, Th1, Th2, Th17, and regulatory T cells (Treg) have been extensively studied [18-20]. Th1 mainly secretes IL-2, IL-12, IFN- γ, and TNF- α, promoting the proliferation of Th1, and plays critical roles in the cellular immunity. Furthermore, these cytokines inhibit the proliferation of Th2[21-22]. IFN- γ activates and enhances the phagocytotic property of macrophages and promotes the production of IgG[23-24]. IL-2, IFN- γ and IL-12 can enhance the killing ability of NK cells [25]. IL-2 and IFN- γ synergistically stimulate the proliferation and differentiation of cytotoxic T cells (CTL). On the other hand, TNF directly induces apoptosis of target cells and also promotes inflammatory response[26-27]. Th2 mainly secretes IL-4, IL-5, IL-6, IL-10, and IL-13, which promotes the proliferation of Th2 cells and participates in the activation of B cells. In addition, these cytokines induce humoral immunity and inhibit the proliferation of Th1[28-30]. Th17 induces innate immunity and inflammation by secretion of IL-17 (IL-17A to IL-17F), IL-21, IL-22, IL-26, TNF-α, and other cytokines. Moreover, Th17 induces the occurrence and development of immunepathological damage, especially autoimmune diseases [31-33]. Treg cells exert the immunosuppression by inhibiting the activation and proliferation of CD4+ and CD8+ T cells and function of DC[34], negatively regulating the immune response. The act is performed mainly in two ways: ① Inhibiting the ability of the APC to activate the T cells mainly through the molecules CTLA-4, LAG-3 on the surface of Treg to interact with the CD80, CD86, and MHC on the DC surface, respectively; ② Suppressing effector T cells by secreting TGF-β、IL-10 and IL-35[34]. Generally,cytokines secreted by CD4+ T cells regulate the function of immune cells,monitor the development, differentiation, and function of other immune cells such as CD8+ T cells, B cells, NK cells, DC. Therefore, CD4+ T cells play a key and central role in the immune system. Naïve CD8+ T cells (CD8+ Tn) can develop and differentiate into CD8+ T cells upon stimulation by antigens presented by DC. Consequently, CD8+ T cells can differentiate into CTL that kill pathogen-infected cells and tumor cells through cytolytic molecules, such as perforin and granzyme, and are essential for a cell-mediated antitumor immune response[35-37]. Alternatively, CTLs induce tumor cell apoptosis by promoting the binding of FasL to Fas on the surface of tumor cells [38-39] (Fig. 1).