Выходит 4 номеров в год
ISSN Печать: 2694-4642
ISSN Онлайн: 2694-4650
Indexed in
Toll-like Receptor 2 and 4 in Cancer Immunotherapy: Is Nitric Oxide a Mediator?
Краткое описание
The main function of the immune system is to recognize and eliminate pathogens. Recognition of these organisms is done by binding of evolutionary conserved molecules called pathogen-associated molecular patterns (PAMPs) to specific receptors called pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), which are mainly expressed by immune cells. Tumor cells, which do not produce PAMPs, are therefore able to escape from immune surveillance. Consequently, effective cancer immunotherapies using PRR ligands were developed. Thus, the use of Bacillus Calmette-Guerin (BCG), a TLR-2 ligand, and Taxol, a TLR-4 ligand, have become standard cancer immunotherapies. In our laboratory, we have developed an efficient immunotherapy approach in murine models of colon and breast cancers with a lipid A analog, OM-174. After TLR-4 binding, OM-174 induces immune cell recruitment, inflammatory response activation, cytokine secretion, inducible nitric oxide synthase (iNOS) expression, and nitric oxide (NO) production in tumors. Moreover, although NO is not toxic itself for tumor cells, it could sensitize them to the death-induced by tumor necrosis factor (TNF)-family ligands such as the Fas ligand (FasL), TNF-related apoptosis-inducing ligand (TRAIL), and TNF-α. Thus, NO may play a mediator role in efficient immunotherapies based on TLR-2 and TLR-4 activation.