Molecular and Cell Biology Program, Ohio University , Athens, OH , USA.
Molecular and Cell Biology Program, Ohio University , Athens, OH , USA ; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University , Athens, OH , USA.
Front Immunol. 2014 Jul 22;5:341. doi: 10.3389/fimmu.2014.00341. eCollection 2014.
In the last decade, it has become apparent that toll-like receptor (TLR) signaling can play an important role in ovarian cancer (OC) progression. Interestingly, TLR activation in immune cells can help activate an anti-tumor response, while TLR signaling in tumor cells themselves is often associated with cancer-promoting inflammation. For example, it has been shown that TLR activation in dendritic cells can result in more effective antigen presentation to T cells, thereby favoring tumor eradication. However, aberrant TLR expression in OC cells is associated with more aggressive disease (likely due to recruitment of pro-tumoral leukocytes to the tumor site) and has also been implicated in resistance to mainstream chemotherapy. The delicate balance of TLR activation in the tumor microenvironment in different cell types altogether help shape the inflammatory profile and outcome of tumor growth or regression. With further studies, specific activation or repression of TLRs may be harnessed to offer novel immunotherapies or adjuvants to traditional chemotherapy for some OC patients. Herewith, we review recent literature on basic and translational research concerning therapeutic targeting of TLR pathways for the treatment of OC.
在过去的十年中,人们已经明显认识到 Toll 样受体 (TLR) 信号通路在卵巢癌 (OC) 进展中可能发挥着重要作用。有趣的是,免疫细胞中的 TLR 激活有助于激活抗肿瘤反应,而肿瘤细胞本身的 TLR 信号通路通常与促进癌症的炎症有关。例如,已经表明树突状细胞中的 TLR 激活可以导致更有效地向 T 细胞呈递抗原,从而有利于肿瘤的清除。然而,OC 细胞中 TLR 的异常表达与更具侵袭性的疾病相关(可能是由于招募促肿瘤白细胞到肿瘤部位),并且也与对主流化疗的耐药性有关。不同细胞类型中 TLR 在肿瘤微环境中的激活的微妙平衡有助于塑造炎症特征,并影响肿瘤生长或消退的结果。随着进一步的研究,TLR 的特定激活或抑制可能被用于为某些 OC 患者提供新的免疫疗法或辅助传统化疗。在此,我们回顾了有关 TLR 通路治疗 OC 的基础和转化研究的最新文献。