Toll-like receptor 7/8 agonist, R848, exhibits antitumoral effects in a breast cancer model

Abstract

Toll-like receptors have been utilized in cancer therapeutic strategies in recent years. To the best of our knowledge, the systemic use of the toll-like receptor 7/8 (TLR7/8) agonist has not been investigated in a breast cancer model. In the current study, tumor growth following drug therapy was examined. Immunofluorescence and TUNEL staining were performed in order to examine the tumor vasculature and apoptosis, respectively. In addition, immunohistochemistry was used to assess HMGB1 in tumor tissues. Activated CD4+ T cells in the peripheral blood were examined by flow cytometry. In the present study, it was identified that the TLR7/8 agonist, R848, exhibited a robust antitumoral effect. R848 reduced tumor vasculature and induced tumor cell apoptosis. In addition, R848 increased high mobility group box 1 expression in tumor tissues and activated CD4+ T cells in the peripheral blood. A synergistic antitumoral effect of R848 and the anti-angiogenic agent, sunitinib, was observed. The present findings suggest that the TLR7/8 agonist may be a potential adjuvant to potentiate the effect of anti-angiogenic therapy.