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Understanding HLA-G driven journey from HPV infection to cancer cervix: Adding missing pieces to the jigsaw puzzle
Journal of Reproductive Immunology ( IF 2.9 ) Pub Date : 2020-10-21 , DOI: 10.1016/j.jri.2020.103205
Ritu Aggarwal 1 , Madhulika Sharma 1 , Navdeep Mangat 1 , Vanita Suri 2 , Tanvi Bhatia 1 , Prashant Kumar 3 , Ranjana Minz 1
Affiliation  

Human Papillomavirus (HPV) is a vital risk-factor for cancer cervix. However, persistent HPV infection results in cervical cancer in only a minority. Probably, HPV subdues the host immune response for persistence, which includes augmentation of HLA-G and plausibly aids in progression to cervical cancer. HLA-G, which comprises of membrane and soluble form, downregulates the host’s immune response and generate tolerance. The current study aimed to analyze both forms of HLA-G in fresh tissue and plasma of women with HPV-infected and uninfected cervix and cancer cervix using Western blot and ELISA. The study cohort included 30 women with cervical carcinoma and equal number with normal cervix and 6 with HPV infected cervix. We observed a significant upregulation of membranous HLA-G expression in HPV infected cervix and cervical carcinoma (P < 0.001).

Interestingly, the pairwise comparison of HLA-G tissue protein expression of the normal cervix and cervical carcinoma, as well as the normal cervix with HPV infected cervix, was significant (P < 0.001). Levels of soluble HLA-G were significantly raised in carcinoma cervix. We observed a progressive increase in HLA-G protein expression in HPV infected cervix and cervical carcinoma. These findings compel us to hypothesize that the upregulation of HLA-G expression favors the persistence of HPV in a microenvironment of a submissive host response. This progressive upregulation further leads to cervical cancer. Thus elimination of HPV infection seems to be a desirable proposition to prevent cervical cancer. In the absence of antiviral therapy for HPV, exploration of HLA-G antibody-based therapeutic strategies appear promising.



中文翻译:

了解 HLA-G 驱动的从 HPV 感染到宫颈癌的旅程:在拼图游戏中添加缺失的部分

人乳头瘤病毒 (HPV) 是宫颈癌的重要危险因素。然而,持续的 HPV 感染仅在少数情况下会导致宫颈癌。很可能,HPV 抑制了宿主免疫反应的持续性,其中包括 HLA-G 的增加,并且可能有助于宫颈癌的进展。HLA-G 由膜和可溶形式组成,可下调宿主的免疫反应并产生耐受性。目前的研究旨在使用蛋白质印迹和 ELISA 分析感染 HPV 和未感染宫颈以及宫颈癌的女性新鲜组织和血浆中的两种形式的 HLA-G。该研究队列包括 30 名患有宫颈癌的女性,她们与正常宫颈的人数相等,而 6 名患有 HPV 感染的宫颈。我们观察到 HPV 感染的宫颈癌和宫颈癌中膜 HLA-G 表达的显着上调(P < 0.001)。

有趣的是,正常宫颈和宫颈癌的 HLA-G 组织蛋白表达以及正常宫颈与 HPV 感染的宫颈的 HLA-G 组织蛋白表达的成对比较是显着的(P < 0.001)。宫颈癌中可溶性 HLA-G 的水平显着升高。我们观察到 HPV 感染的宫颈癌和宫颈癌中 HLA-G 蛋白表达逐渐增加。这些发现迫使我们假设 HLA-G 表达的上调有利于 HPV 在顺从宿主反应的微环境中持续存在。这种渐进的上调进一步导致宫颈癌。因此,消除 HPV 感染似乎是预防宫颈癌的理想主张。在缺乏针对 HPV 的抗病毒治疗的情况下,探索基于 HLA-G 抗体的治疗策略似乎很有希望。

更新日期:2020-10-30
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