Fig. 1

Interaction between immune cells and CSCs in the immunosuppressive tumor microenvironment. a CSCs impair recruiting and maturation of DCs in tumor sites or use TGF-β signaling to induce DC differentiation into DCregs. b CSCs-derived TGF-β/CCLs induce the differentiation of M1 macrophage to M2 phenotype ones vs. M2 macrophages induce EMT and stemness in CSCs. c CSCs-derived TGF-β recruits MDSCs in tumor sites and reciprocally, MDSCs support CSCs stemness and propagation. d CSCs-derived TGF-β also recruits Tregs in tumor sites and reciprocally, Tregs-derived VEGF induces angiogenesis supporting CSCs survival and EMT. e PD-L1 + CSCs suppress T cells activation or induce their differentiation into Tregs-supporting tumors. f CSCs-derived IL-6 and TGF-β downregulate NK-activating receptors, and also, CSCs suppress NK cells activation through re-expression of MHC-II or shedding of MIC A/B and CD155-suppressing activating receptors