Toll-like receptors (TLRs) are a group of transmembrane receptors that recognize molecular motifs of pathogen origin and activate immune response. Although TLRs were first identified in immune system cells, recent studies show they can also be expressed in
tumor cells. TLR3 recognizes dsRNA or its synthetic
ligand poly (I: C) and is responsible primarily for the defense against
viral infections. Recent studies showed that TLR3 can trigger apoptosis in
cancer cell. Furthermore, other dsRNA binding receptors (MDA5 and RIG-I), localized in cytoplasm, can also bind
poly (I: C) and therefore contribute to this effect. With TLR3's capacity to induce apoptosis and activate the immune system at the same time, TLR3
ligands are an attractive therapeutic option for treatment of
cancer. Novel
therapies include combining
poly (I: C) with other components such as chemotherapeutics, apoptosis enhancers, other TLR
ligands and
peptides activating the immune system. Slightly modified TLR3 agonists (Ampligen®, Hiltonol®, poly IC-LC) are already being used in clinical studies for
cancer therapy as single agents or in combination with other drugs. On the other hand, latest studies forewarn that TLR3 activation can also have
tumor promoting role so it is crucial to identify the terms by which TLR3 has pro-
tumor/anti-
tumor effect in order to safely implement TLR3
ligand based
therapy into clinical trials.