Yu Li, Wang Liantang, Chen Shangwu
Department of Pathology, Sun Yat-sen University, Guangzhou, Republic of China.
Biochim Biophys Acta. 2013 Apr;1835(2):144-54. doi: 10.1016/j.bbcan.2012.10.006. Epub 2012 Dec 8.
As a major class of pattern-recognition receptors, Toll-like receptors (TLRs) play a critical role in defense against invading pathogens. Increasing evidence demonstrates that, in addition to infection, TLRs are involved in other important pathological processes, such as tumorigenesis. Activation of TLRs results in opposing outcomes, pro-tumorigenic effects and anti-tumor functions. TLR signaling can inhibit apoptosis and promote chronic inflammation-induced tumorigenesis. TLR activation in tumor cells and immune cells can induce production of cytokines, increase tumor cell proliferation and apoptosis resistance, promote invasion and metastasis, and inhibit immune cell activity resulting in tumor immune escape. In contrast, the engagement of other TLRs directly induces growth inhibition and apoptosis of tumor cells and triggers activation of immune cells enhancing anti-tumor immune responses. Thus, the interpretation of the precise function of each TLR in tumors is very important for targeting TLRs and using TLR agonists in tumor therapy. We review the role of TLR signaling in tumors and discuss the factors that affect outcomes of TLR activation.
作为一类主要的模式识别受体，Toll样受体（TLRs）在抵御病原体入侵中发挥着关键作用。越来越多的证据表明，除了感染之外，TLRs还参与其他重要的病理过程，如肿瘤发生。TLRs的激活会导致相反的结果，即促肿瘤效应和抗肿瘤功能。TLR信号传导可抑制细胞凋亡并促进慢性炎症诱导的肿瘤发生。肿瘤细胞和免疫细胞中的TLR激活可诱导细胞因子产生，增加肿瘤细胞增殖和抗凋亡能力，促进侵袭和转移，并抑制免疫细胞活性，导致肿瘤免疫逃逸。相反，其他TLRs的激活直接诱导肿瘤细胞生长抑制和凋亡，并触发免疫细胞激活，增强抗肿瘤免疫反应。因此，准确解读每个TLR在肿瘤中的具体功能对于靶向TLRs并在肿瘤治疗中使用TLR激动剂至关重要。我们综述了TLR信号传导在肿瘤中的作用，并讨论了影响TLR激活结果的因素。
