TLR5配体作为新型抗肿瘤靶点的研究进展

Research Progress of TLR5 Ligand as a Novel Antitumor Target

利用宿主机体本身的免疫反应和炎症反应治疗肿瘤是一种很有前景的治疗策略。越来越多的证据表明,Toll样受体(TLRs)是先天免疫中的关键受体,在癌症的发生和发展过程中发挥着重要作用,不同的Toll样受体的抗肿瘤效果可能不同。它们能够通过启动先天免疫反应和适应性T细胞免疫来刺激抗肿瘤免疫的发生,也可以通过激活炎症反应达到影响肿瘤发展的目的,因此Toll样受体作为潜在的治疗靶点受到越来越多的关注,其激动剂因其抗肿瘤潜力而成为了研究热点。在此背景下,鼠伤寒沙门氏菌的鞭毛蛋白已经被确定为一种潜在的肿瘤治疗药物,能够诱导肿瘤消退,这种治疗效果被认为是由TLR家族模式识别受体TLR5介导的细菌抗原性和宿主先天免疫反应的激活所介导的,但其确切的作用机制目前并不完全清楚。目前的研究结果表明,TLR5能够特异性地识别鞭毛蛋白,激活体内相关通路,诱导机体内的免疫反应和炎症反应,募集趋化因子和促炎因子,进而影响肿瘤进程。该综述旨在讨论TLR5的配体—细菌鞭毛蛋白的抗肿瘤作用以及作为新型抗肿瘤靶点的可能性。

It is a promising therapeutic strategy to treat tumors by using the host organism’s own immune response and inflammatory response.More and more evidence shows that TLRs(Toll-like receptors)are the key receptors in innate immunity and play an important role in the occurrence and development of cancer.Different Toll-like receptors may have different anti-tumor effects,and they can stimulate the occurrence of anti-tumor immunity by initiating innate immune response and adaptive T cell immunity.It can also affect the development of tumor by activating inflammatory reaction,so TLR as a potential therapeutic target has attracted more and more attention,and its agonist has been actively studied for its anti-tumor potential.In this context,the flagellin of Salmonella typhimurium has been identified as a potential tumor therapeutic agent capable of inducing tumor regression,and this therapeutic effect is thought to be mediated by the TLR family pattern recognition receptor TLR5-mediated bacterial antigenicity and mediated by the activation of the host innate immune response,but its exact mechanism of action is not fully understood.The current research results show that TLR5 can specifically recognize flagellin,activate related pathways in vivo,induce immune and inflammatory responses in the body,recruit chemokines and pro-inflammatory factors,and then affect tumor progression.This review aims to discuss the antitumor effects of bacterial flagellin,a ligand of TLR5,and its potential as a novel antitumor target.