title: 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.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Sisi
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000819:agonists; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011758:Pyrroles / Q000494:pharmacology; D000077210:Sunitinib; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051200:Toll-Like Receptor 8 / Q000819:agonists; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D007093:Imidazoles; D007211:Indoles; D008562:Membrane Glycoproteins; D011758:Pyrroles; C552579:TLR8 protein, mouse; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C402365:resiquimod; D000077210:Sunitinib