Sorafenib augments the therapeutic efficacy of ACT by inhibiting STAT3 expression and downregulating immunosuppressive factors in tumor cells and tumor microenvironment.

Downregulation of immunosuppressive factors, including TGF-β, IL-10, CCL2/MCP-1 and VEGF, lowers the populations of both Tregs and MDSCs. Transferred CD8+ T cells show better activation and killing effects due to declined Tregs and MDSCs. Furthermore, more transferred CD8+ T cells accumulate in tumors and survive longer, so that enhanced therapeutic responses can be achieved.