Toll-like receptors (TLRs) are a family of highly conserved germline-encoded
pattern-recognition receptors that are essential for host immune responses. TLR
ligands represent a promising class of immunotherapeutics or
vaccine adjuvants with the potential to generate an effective antitumor immune response. The TLR7/8 agonists have aroused interest because they not only activate antigen-presenting cells but also promote activation of T and natural killer (NK) cells. However, the exact mechanism by which stimulation of these TLRs promotes immune responses remains unclear, and different TLR7/8 agonists have been found to induce different responses. In this study, we demonstrate that both
gardiquimod and
imiquimod promote the proliferation of murine splenocytes, stimulate the activation of splenic T, NK and natural killer T (NKT) cells, increase the cytolytic activity of splenocytes against B16 and MCA-38 tumor cell lines, and enhance the expression of costimulatory molecules and
IL-12 by macrophages and bone marrow-derived dendritic cells (DCs). In a murine model, both agonists improved the antitumor effects of
tumor lysate-loaded DCs, resulting in delayed growth of subcutaneous
B16 melanoma tumors and suppression of pulmonary
metastasis. Further, we found that
gardiquimod demonstrated more potent antitumor activity than
imiquimod. These results suggest that TLR7/8 agonists may serve as potent innate and adaptive immune response modifiers in
tumor therapy. More importantly, they can be used as
vaccine adjuvants to potentiate the efficiency of DC-based
tumor immunotherapy.