Shi Ming, Chen Xi, Ye Kangruo, Yao Yuanfei, Li Yu
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Medicine (Baltimore). 2016 Jun;95(25):e3951. doi: 10.1097/MD.0000000000003951.
Toll-like receptors (TLRs), as the most important pattern recognition receptors in innate immunity, play a pivotal role in inducing immune response through recognition of microbial invaders or specific agonists. Recent studies have suggested that TLRs could serve as important regulators in the development of a variety of cancer. However, increasing evidences have shown that TLRs may display quite opposite outcomes in cancer development. Although several potential therapeutic Toll-like receptor ligands have been found, the mechanism and therapy prospect of TLRs in cancer development has to be further elucidated to accelerate the clinical application. By performing a systematic review of the present findings on TLRs in cancer immunology, we attempted to evaluate the therapeutic potential of TLRs in cancer therapy and elucidate the potential mechanism of cancer progress regulated by TLR signaling and the reported targets on TLRs for clinical application. An electronic databases search was conducted in PubMed, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database from their inception to February 1, 2016. The following keywords were used to search the databases: Toll-like receptors, cancer therapy, therapeutic target, innate immunity. Of 244 studies that were identified, 97 nonrelevant studies were excluded. In total, 147 full-text articles were assessed, and from these, 54 were excluded as they did not provide complete key information. Thus, 93 studies were considered eligible and included in the analysis. According to the data from the included trials, 14 TLR ligands (77.8%) from 82 studies have been demonstrated to display antitumor property in various cancers, whereas 4 ligands (22.2%) from 11 studies promote tumors. Among them, only 3 TLR ligands have been approved for cancer therapy, and 9 ligands were in clinical trials. In addition, the potential mechanism of recently reported targets on TLRs for clinical application was also evaluated in this review. We show that targeting TLRs in cancer immunotherapy is a promising strategy for cancer therapy, and the specific TLR ligands, either alone or combination, exhibit antitumor potential.
Toll样受体（TLRs）作为天然免疫中最重要的模式识别受体，通过识别微生物入侵者或特定激动剂在诱导免疫反应中起关键作用。最近的研究表明，TLRs可能是多种癌症发展中的重要调节因子。然而，越来越多的证据表明，TLRs在癌症发展中可能呈现完全相反的结果。尽管已经发现了几种潜在的治疗性Toll样受体配体，但TLRs在癌症发展中的机制和治疗前景仍需进一步阐明，以加速其临床应用。通过对目前癌症免疫学中关于TLRs的研究结果进行系统综述，我们试图评估TLRs在癌症治疗中的治疗潜力，并阐明由TLR信号调控的癌症进展的潜在机制以及已报道的用于临床应用的TLRs靶点。在PubMed、中国科学期刊数据库和中国生物医学文献数据库中进行了电子数据库检索，检索时间从各数据库建库至2016年2月1日。使用以下关键词检索数据库：Toll样受体、癌症治疗、治疗靶点、天然免疫。在识别出的244项研究中，排除了97项不相关的研究。总共评估了147篇全文文章，其中54篇因未提供完整关键信息而被排除。因此，93项研究被认为符合条件并纳入分析。根据纳入试验的数据，82项研究中的14种TLR配体（77.8%）已被证明在各种癌症中具有抗肿瘤特性，而11项研究中的4种配体（22.2%）促进肿瘤生长。其中，只有3种TLR配体已被批准用于癌症治疗，9种配体正在进行临床试验。此外，本综述还评估了最近报道的用于临床应用的TLRs靶点的潜在机制。我们表明，在癌症免疫治疗中靶向TLRs是一种有前景的癌症治疗策略，特定的TLR配体单独或联合使用均具有抗肿瘤潜力。
