Lopes Jorge André Gomes, Borges-Canha Marta, Pimentel-Nunes Pedro
Jorge André Gomes Lopes, Marta Borges-Canha, Pedro Pimentel-Nunes, Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.
World J Hepatol. 2016 Jan 28;8(3):162-82. doi: 10.4254/wjh.v8.i3.162.
Hepatocarcinoma (HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long ago. Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis. An effective innate immunity response relies on the toll-like receptors (TLR) found in several different liver cells which, through different ligands and many signaling pathways can elicit, not only a pro-inflammatory but also an oncogenic or anti-oncogenic response. Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets. We performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March 2015. TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNA-damages and to cell survival. However, pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis. TLR3 has a well-known protective role influencing crucial processes like angiogenesis, cell growth or proliferation. TLR4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed. TLR9's influence on carcinogenesis is also controversial and despite a potential anti-cancer capacity, a pro-tumorigenic role is more likely. Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported. As therapeutic targets, TLRs are already in use and have a great potential. In conclusion, TLRs have been shown to be an interesting influence on the HCC's microenvironment, with TLR3 clearly determining an anti-tumour influence. TLR4 and TLR9 are considered to have a positive relationship with tumour development even though, in each of them anti-tumorigenic signals have been described. TLR2 presents a more ambiguous role, possibly depending on the stage of the inflammation-HCC axis.
肝癌（HCC）是全球一种高度流行的癌症，其炎症背景早在很久以前就已确立。最近的研究表明，固有免疫与肝癌的发生密切相关。有效的固有免疫反应依赖于在几种不同肝细胞中发现的Toll样受体（TLR），这些受体通过不同的配体和许多信号通路，不仅可以引发促炎反应，还能引发致癌或抗癌反应。我们的目的是研究TLR在肝脏肿瘤发生中的作用，以及它们作为潜在治疗靶点的价值。我们对PubMed进行了系统综述，搜索截至2015年3月研究HCC与TLR之间关系的原始文章。TLR2似乎是一种基本的应激传感器，因为它的缺失显示出积累DNA损伤和细胞存活的增强趋势。然而，由于TLR2的上调也与肿瘤发生增强有关，其相关通路仍未完全了解。TLR3具有众所周知的保护作用，影响血管生成、细胞生长或增殖等关键过程。TLR4作为一种有趣的上皮-间质转化诱导剂和细胞存活促进剂，可能诱导肝癌发生，尽管已经观察到其具有抗癌作用。TLR9对肿瘤发生的影响也存在争议，尽管它具有潜在的抗癌能力，但更可能具有促肿瘤作用。已经发现一些TLR存在基因多态性，并且报道了其对肝癌风险的影响。作为治疗靶点，TLR已经在使用中并且具有很大的潜力。总之，TLR已被证明对肝癌微环境有有趣的影响，其中TLR3明显具有抗肿瘤影响。TLR4和TLR9被认为与肿瘤发展呈正相关，尽管在它们各自中都已描述了抗肿瘤信号。TLR2呈现出更模糊的作用，可能取决于炎症-肝癌轴的阶段。
