No abstract

The toll-like receptor (TLR) system constitutes a pylogenetically ancient, evolutionary conserved, archetypal pattern recognition system, which underpins pathogen recognition by and activation of the immune system. Toll-like receptor agonists have long been used as immunoadjuvants in anti cancer immunotherapy. However, TLRs are increasingly implicated in human disease pathogenesis and an expanding body of both clinical and experimental evidence suggests that the neoplastic process may subvert TLR signalling pathways to advance cancer progression. Recent discoveries in the TLR system open a multitude of potential therapeutic avenues. Extrapolation of such TLR system manipulations to a clinical oncological setting demands care to prevent potentially deleterious activation of TLR-mediated survival pathways. Thus, the TLR system is a double-edge sword, which needs to be carefully wielded in the setting of neoplastic disease. METHODSReferenced papers were identified using multiple electronic searches of the Medline database with the keywords (alone or in combination): toll-like receptors (TLRs), cancer, TLR ligands, NFkB, innate immunity, acquired immunity and immunotherapy. The search strategy incorporated MESH terms, and results were evaluated for sensitivity and specificity. Additional articles were identified from the references of retrieved papers. Papers were included on the basis of evidence supporting individual points.