Immunotherapy of tumors with neuroimmune ligand capsaicin.

Red chili pepper (Capsicum frutescens) is a highly consumed spice throughout the world. Its principal pungent ingredient is the phenol capsaicin (8-methyl-N-vanillyl-6-nonenamide). Capsaicin causes neurogenic inflammation and has analgesic and anti-inflammatory activities. We have observed previously that dendritic cells, a key cell type in immune responses, have the receptor for capsaicin, and engagement of this receptor has powerful immune consequences. In this study, we demonstrate that intratumoral administration of capsaicin into a preexisting tumor results in retarded progression of the injected tumor regardless of whether the tumor is at its early or late stage. Furthermore, it leads to significant inhibition of growth of other, uninjected tumors in the same animal. Capsaicin-elicited immunity is shown to be T cell-mediated and tumor-specific. These results reflect the immunological potency of a neurological ligand in modulating immune response against an established tumor.