Toll-like Receptor 7/8 Agonists Exert Antitumor Effect in a Mouse Melanoma Model.

Abstract

: Toll-like receptors (TLRs) are pattern recognition receptors with an essential role in regulating both the innate and adaptive immune response. Given their pleiotropic effects in mounting an immune response, previous studies have proposed targeting these TLRs might render alternative strategies for cancer therapy. Synthetic immune response modifiers, such as imidazoquinolines, stimulate the immune cells by activating Toll-like receptors, particularly TLR7/8 receptors, consequently mounting an immune response. Agonists of this class activate, via TLR-mediated signaling, dendritic and B cells, as well as myeloid cells and T cells, thus exhibiting good prospects for cancer immunotherapy. In the present study, we sought to evaluate the effect of imiquimod and gardiquimod, two TLR 7 and 7/8 agonists, respectively, on tumor growth and phenotype of NK cells associated with melanoma.: We generated a syngeneic model of melanoma in C57BL/6J mice by subcutaneously injecting murine melanoma cells and monitoring tumor growth. Starting on day 8 or 14, we applied TLR agonists either intratumorally or topically and followed the tumor dynamics and NK cell-associated pattern.: Our results suggest that both TLR agonists displayed an antitumor effect along with a phenotypically activated profile of NK cells. Both imiquimod and gardiquimod treatment inhibited tumor growth, with gardiquimod showing an increased potency compared to imiquimod.: This implies that TLR agonists like imiquimod and gardiquimod could serve as neoadjuvant, adjuvant, or complementary immunotherapeutic agents in melanoma therapy.