1.2 DC is the initial factor inducing adaptive tumor immunity
DCs were first reported in skin by Langerhans in 1868. Steinman and Cohn later described DC in peripheral lymphoid organs in 1973. DCs form an essential link between innate immunity and adaptive immunity. More importantly, DCs induce the occurrence of adaptive immunity[40].
DC represents a complex heterogeneous population of antigen-presenting cell with significant phenotypic heterogeneity and functional plasticity. DCs can be divided into two main subpopulations: conventional DC (cDC) and plasmacytoid DC (pDC). DCs are derived from bone marrow and migrate through blood circulation to lymphoid tissues such as lymph nodes and spleen and non-lymphoid tissues such as skin, lung, and intestine [41]. cDCs are further subdivided into type 1 cDC and type 2 cDC [42-43]. cDC1 can cross-present antigens and trigger an antitumor immune response and, thus, often referred to as cross-presenting DCs. cDC1 presents tumor antigen to CD8+ Tn cells via the MHCI, activating the initial immune response [44-45]. After activating CD8+ Tn, CD8+ Tn gradually develop and differentiate into immune memory cells, such as Tscm, Tcm, Tem, and Tte, inducing the occurrence of recall response by re-stimulation of past antigen encounters. The quick responses to the secondary stimulation of antigen form a large number of specific immune cells in a short time and effectively kill tumor cells[46-47]. It is worth noting that among several antigen-presenting cells, only DC can stimulate the initial immune response and induce Tn to produce an immune response targeting “new” antigens. It is speculated that the damage of DC is closely related to refractory tumors. cDC1 plays a key role in lung immunity[48]. On the other hand, cDC2 is a major DC subpopulation in different human tissues and organs. Besides, cDC2 presents tumor antigens to CD4+ Tn cells via the MHCII and activates the initial immune response of CD4 + Tn. Like CD8+ Tn, after activation, CD4+Tn also gradually develop and differentiate into immune memory cells such as Tscm, Tcm, Tem, and Tte, forming a memory immune response to coordinate the immune response and homeostasis[49]. In addition, pDC are key players in antiviral immunity. The pDCs can produce high levels of type I interferon (IFN), promoting innate and adaptive immunity[50] (Figure 1). The IFN is considered the key natural immune defense of the body against pathogen infection. Furthermore, IFN inhibits the proliferation of tumor cells and regulates immunity [51-52].