Toll-like receptors (TLRs) comprise a family of 13 surface or endosomal receptors that recognize ligands that are broadly shared by pathogens, collectively referred to as pathogenassociated molecular pattern (PAMP) molecules. PAMPs activate DCs and stimulate the release of cytokines and chemokines, thus facilitating the development of adaptive immune responses. In humans, TLR8 is distinguished from other endosomally-expressed TLRs by its unique appearance on mDCs, monocytes, and natural killer (NK) cells. The natural ligand of TLR8 is foreign single-stranded RNA; engagement triggers cellular activation and maturation, including the release of Th1-polarizing cytokines. Based on a small genetic deletion in the murine TLR8 gene, the activity of TLR8 agonists in mice is significantly attenuated compared to that in humans and other species. Consequently, the in vivo biological activity of TLR8 agonists has not been extensively studied to date. Nonetheless, the specific expression of TLR8 within human myeloid cells offers unique opportunities for anticancer therapy.
Monk B J, et al. Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemo-immunotherapy[J]. Clinical Cancer Research, 2016: clincanres. 1453.2016.