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. 2021 Jun 9;9:680100. doi: 10.3389/fcell.2021.680100

FIGURE 1.

FIGURE 1

CSCs create ITAIMs mainly through four SRSs: The Notch-NF-κB axis, HH, Wnt and STAT3 pathways. Exogenous Wnt and HH proteins enter CSCs to activate corresponding SRSs. Wnt signaling acts on CD103+ DCs by inducing the transcription inhibitor ATF3. The reduction in CCL4, CXCL-9 and -10 reduces CD8+ T cell activation and infiltration. HH signaling recruits TAMs and immunosuppresses MDSCs by releasing CCL2 and CCL3. Notch-NF-κB axis signaling mainly regulates Tregs, MDSCs and T cells through a series of cytokines in the TAIM. Activated STAT3 signaling can promote the accumulation of immunosuppressive CD163+ TAMs through IL-1 and IL-10. It also downregulates the expression of CXCL-10 and reduces the cytotoxicity of NK cells. The activation of STAT3 inhibits the expression of type I IFN signaling and antitumor immune responses. The HH and Notch-NF-κB axis and STAT3 signaling pathways can also promote PD-L1 expression and suppress the immune response.