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).