Curcumin combined with FAPac vaccine elicits effective antitumor response by targeting indolamine-2,3-dioxygenase and inhibiting EMT induced by TNF-α in melanoma

Fibroblast activation protein alpha (FAP alpha) is a potential target for cancer therapy. However, elimination of FAP alpha+ fibroblasts activates secretion of IFN-gamma and TNF-alpha. IFN-gamma can in turn induce expression indolamine-2,3-dioxygenase (IDO), thereby contributing to immunosuppression, while TNF-alpha can induce EMT. These two reactive effects would limit the efficacy of a tumor vaccine. We found that curcumin can inhibit IDO expression and TNF-alpha-induced EMT. Moreover, FAP alpha c vaccine and CpG combined with curcumin lavage inhibited tumor growth and prolonged the survival of mice implanted with melanoma cells. The combination of FAP alpha c vaccine, CpG and curcumin stimulated FAP alpha antibody production and CD8+ T cell-mediated killing of FAP alpha-expressing stromal cells without adverse reactive effects. We suggest a combination of curcumin and FAP alpha c vaccine for melanoma therapy.