Figure 3.

Reciprocal natural killer (NK)—dendritic cell (DC) cross talk. Upon activation by target tumor cells or cytokines, NK cells produce IFN-γ and tumor necrosis factor (TNF)-α that can promote DC maturation. DC maturation is also strongly dependent on the engagement of activating receptors on NK cells such as NKp30 and NKG2D. Mature DCs (mDCs) will in turn produce interleukin (IL)-12, IL-15, and IL-18, which enhance cytotoxicity and IFN-γ secretion of NK cells. NK cells can also distinguish immature (iDC) and mDCs through activating NKp30 and inhibitory killer cell immunoglobulin-like receptors and NKG2A/CD94 and eliminate immature DCs (iDCs), thereby maintaining the quality of the mDC population (DC editing). NK-cell cytotoxicity can be further augmented by IFN-α secreted by plasmacytoid DCs (pDCs). NK-induced tumor cell lysis provides antigens, which can be taken up by DCs for antigen presentation. Once maturated, antigen-loaded mDCs will migrate into tumor-draining lymph nodes, cross-present tumor antigens to naïve T cells, and induce their differentiation toward tumor-specific CD8⁺ cytotoxic T cells and CD4⁺ T helper 1 (Th1) cells.