Husseinzadeh Nader, Davenport Sara Madison
University of Cincinnati College of Medicine, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, 231 Albert Sabin Way, Cincinnati, OH 45267-0526, USA.
University of Cincinnati College of Medicine, Department of Obstetrics and Gynecology, 231 Albert Sabin Way, Cincinnati, OH 45267-0526, USA.
Gynecol Oncol. 2014 Nov;135(2):359-63. doi: 10.1016/j.ygyno.2014.08.013. Epub 2014 Aug 16.
The Toll-like receptors (TLRs) have been implicated in inflammation, innate immunity and cancer. The goal of this paper is to review the available published research about Toll-like receptors and their roles in gynecologic malignancies.
A Medline search was conducted and published articles from the late 1990s to the present (2014) were reviewed using search phrases, Toll-like receptors and cervical, endometrial and ovarian cancers.
TLR4 and TLR5 are commonly absent in normal cervix, however TLR5 expression is strong in high grade cervical dysplasia as well as invasive cancer. The expression of TLR3 and TLR4 is low in endometrial cancer. TLR2, TLR3, TLR4 and TLR5 are highly expressed in normal and neoplastic ovarian epithelium. TLR3 has been shown to have a dual function: it can contribute to tumor elimination by upregulation of interferons α and β (INF) and natural killer cell (NK) activation or it can indirectly contribute to tumor progression.
Inflammation is an essential element in tumorigenesis. Toll-like receptors can trigger an inflammatory response and cell survival in the tumor micro-environment. TLRs are critical immunomodulators that may play an important role in the development of gynecologic cancers. Currently TLR agonists are being investigated for a potential role as an adjuvant in the treatment of gynecologic malignancies.
Toll样受体(TLRs)与炎症、先天免疫及癌症有关。本文旨在综述已发表的关于Toll样受体及其在妇科恶性肿瘤中作用的研究。
进行了Medline检索,并使用检索词“Toll样受体”以及“宫颈癌、子宫内膜癌和卵巢癌”对20世纪90年代末至2014年发表的文章进行了综述。
正常宫颈中通常不存在TLR4和TLR5,但在高级别宫颈发育异常及浸润性癌中TLR5表达强烈。子宫内膜癌中TLR3和TLR4的表达较低。TLR2、TLR3、TLR4和TLR5在正常及肿瘤性卵巢上皮中高表达。TLR3已被证明具有双重功能:它可通过上调α和β干扰素(INF)以及激活自然杀伤细胞(NK)来促进肿瘤清除,或者间接促进肿瘤进展。
炎症是肿瘤发生的一个重要因素。Toll样受体可在肿瘤微环境中触发炎症反应和细胞存活。TLRs是关键的免疫调节因子,可能在妇科癌症的发展中起重要作用。目前正在研究TLR激动剂作为辅助剂在妇科恶性肿瘤治疗中的潜在作用。