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.

Induction of tumor regression by intratumoral STING agonists combined with anti–programmed death‐L1 blocking antibody in a preclinical squamous cell carcinoma model

“…To investigate this, we assessed the ability of CDNs to slow primary tumor growth compared to PBS or R848, a TLR7/8 agonist with antitumor activity. [19][20][21] We previously developed synthetic CDNs that were optimized as adjuvants with vaccines, so we used both natural CDG and the synthetically modified RR-CDG in these studies. Both CDG and RR-CDG treated tumors showed significantly slower rates of primary tumor growth ( Figure 1A) and enhanced antitumor activity when compared to PBS control (p < .001) and TLR7/8 agonist (R848)-treated mice (p < .05).…”

Anti-tumor Activity of Toll-Like Receptor 7 Agonists

“…So combination therapy is necessitated. Resiquimod exhibited a robust anti-tumor activity in a mouse breast cancer model, combining resiquimod with sunitinib, an antineoplastic agent, largely inhibited the growth of breast cancer cells, and attenuated the immunosuppressive effects of sunitinib (Yin et al, 2015). Cutaneous T-cell lymphoma is malignant tumor of the immune system caused by a mutation of T cells.…”

Therapeutic vaccine to cure large mouse hepatocellular carcinomas

“…In addition to TLR4 ligands, TLR7/8 agonists such as R848 (Resiquimod) have also been demonstrated to promote antitumor immune responses [ 26 , 27 ]. A related TLR7 agonist, imiquimod, has been used for the topical treatment of various epidermal malignancies [ 27 , 28 ].…”