Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
IUBMB Life. 2021 Jan;73(1):10-25. doi: 10.1002/iub.2412. Epub 2020 Nov 20.
At the forefront of the battle against pathogens or any endogenously released molecules, toll-like receptors (TLRs) play an important role as the most noble pattern recognition receptors. The ability of these receptors in distinguishing "self" and "non-self" antigens is a cornerstone in the innate immunity system; however, misregulation links inflammatory responses to the development of human cancers. It has been known for some time that aberrant expression and regulation of TLRs not only endows cancer cells an opportunity to escape from the immune system but also supports them through enhancing proliferation and angiogenesis. Over the past decades, cancer research studies have witnessed a number of preclinical and clinical breakthroughs in the field of TLR modulators and some of the agents have exceptionally performed well in advanced clinical trials. In the present review, we have provided a comprehensive review of different TLR agonists and antagonists and discuss their limitations, toxicities, and challenges to outline their future incorporation in cancer treatment strategies.
在与病原体或任何内源性释放分子的斗争中, Toll 样受体 (TLR) 作为最优秀的模式识别受体发挥着重要作用。这些受体区分“自我”和“非自我”抗原的能力是先天免疫系统的基石;然而,炎症反应的失调与人类癌症的发展有关。TLRs 的异常表达和调节不仅使癌细胞有机会逃避免疫系统,而且通过增强增殖和血管生成来支持它们,这一点已经为人所知了一段时间。在过去的几十年中,癌症研究在 TLR 调节剂领域取得了许多临床前和临床突破,一些药物在高级临床试验中表现出色。在本综述中,我们全面回顾了不同的 TLR 激动剂和拮抗剂,并讨论了它们的局限性、毒性和挑战,以概述它们在癌症治疗策略中的未来应用。