Fig. 3.

The role of hypoxia and stromal cells infiltration in sorafenib resistance. (a) The role of HIF family in hypoxia-mediated sorafenib resistance. (b) The interaction between CAFs and HCC cells under sorafenib-induced hypoxia. (c) Sorafenib-induced hypoxia and HCC cells debris shape an immunosuppressive HCC microenvironment by recruiting BMDCs, Tregs and TAMs, promoting M2 polarization and educating PBNs into TANs. (d) EMT process and tumor plasticity are negatively associated with the TAMs infiltration, while the stemness among different EMT intermediate states keep the same. Abbreviation: CAFs, cancer-associated fibroblasts; PBNs, peripheral blood neutrophils; BMDCs, bone marrow-derived cells; TAMs, tumor-associated macrophages; TANs, tumor-associated neutrophils; Tregs, T regulatory cells.