Vacchelli Erika, Eggermont Alexander, Sautès-Fridman Catherine, Galon Jérôme, Zitvogel Laurence, Kroemer Guido, Galluzzi Lorenzo
Institut Gustave Roussy; Villejuif, France ; Université Paris-Sud/Paris XI; Le Kremlin-Bicêtre; Paris, France ; INSERM, U848; Villejuif, France.
Oncoimmunology. 2013 Aug 1;2(8):e25238. doi: 10.4161/onci.25238. Epub 2013 Jun 10.
Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of , we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.
Toll样受体（TLRs）长期以来因其在接触脂多糖（LPS）和双链RNA等保守微生物成分时引发先天免疫反应的能力而闻名。最近，这类模式识别受体家族在引发抗癌免疫反应中被认为起着关键作用，这引发了人们对基于天然或合成TLR激动剂的免疫化学治疗方案开发的兴趣。尽管有如此强烈的临床前和临床研究浪潮，但目前美国食品药品监督管理局（FDA）仅批准了三种TLR激动剂用于癌症患者：卡介苗（BCG），一种减毒株，作为TLR2/TLR4混合激动剂发挥作用；单磷酰脂质A（MPL），一种的衍生物，作为TLR4的有效激动剂发挥作用；以及咪喹莫特，一种激活TLR7的合成咪唑喹啉。一年前，在《》杂志的8月和9月期，我们描述了TLRs的主要生物学特征，并讨论了评估TLR激动剂在癌症患者中的安全性和治疗潜力的临床研究进展。在这里，我们总结了这一令人兴奋的研究领域的最新进展，重点关注过去13个月内发表的临床前研究以及同期开展的调查TLR激动剂抗肿瘤活性的临床试验。
