Figure 1.

Direct relationship between innate immune cells and HCC. DCs may promote HCC by IDO and IL-10 and inhibit HCC by activating T-cell responses. Macrophages (M1) serve an antitumoral role and are regulated by TNF, while macrophages (M2) play a protumoral role and are regulated by IL-1β, IL-6 and IL-8. HCC can promote M2-polarization of macrophages by signaling pathways or by lncRNA, which contributes to the immunosuppressive microenvironment. HCC cells promote accumulation of neutrophils by secretion of cytokines, such as CXCL1 and CXCL5. In turn, neutrophils promote the development of HCC by MMP9 and HGF. NET derived from neutrophils promote the metastatic potential of HCC. ILCs can secrete IFN-γ to promote hepatocellular tumorigenesis, which may be due to the breakdown of immune tolerance. Tumor-derived soluble MICA (a ligand of NKG2D) or AFP inhibit the functions of NK cells in vitro. TGF-β derived from HCC cells inhibit the activity of NKT cells and NK cells. MDSCs shape the immunosuppressive tumor microenvironment and HCC cells also promote the accumulation of MDSCs. DCs, dendritic cells; M1/M2, M1/M2-type macrophage; N, neutrophils; ILCs, innate lymphoid cells; IDO, indoleamine-2,3-dioxygenase; MMP9, matrix metallopeptidase 9; HGF, hepatocyte growth factor; GM-CSF, granulocyte-macrophage colony stimulating factor; NET, neutrophil extracellular traps; sMICA, soluble major histocompatibility complex class I related chains A; MDSCs, myeloid-derived suppressor cells; NKT cells, natural killer T cells; TGF-β, Transforming growth factor beta; HCC, hepatocellular carcinoma; AFP, α-fetoprotein; lncRNA, long non-coding RNA; TNF, tumor necrosis factor; CXCL, chemokine (C-X-C) ligand motif; CXCR-2, CXC chemokine receptor 2.