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Study of immunologic evasion of human papllomavirus (HPV) Against host immuno-ersponse in patient with cervical cancer

宫颈癌患者人乳头瘤病毒(HPV)抵抗宿主免疫反应的免疫逃避研究

基本信息

批准号：
10671526
负责人：
SASAGAWA Toshiyuki
金额：
$ 1.73万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671526/
关键词：
Human papillomavirus cervical cancer PCR Immunoresponse HLA class II antigen anti HPV antibody ウイルス様粒子(VLP)HLAclassII抗原癌抑制遺伝子免疫 HPV DNA診断

项目摘要

We have recently established the system to detect DNA of most mucosal HPV types using PCR method, which is called LCR-E7 PCR method. Using this method, we tested the prevalence of HPV infection in clinical samples. More than 17 HPV types were identified in normal, condyloma and lower-grade squamous intraepithelial lesions (LSIL). Higher incidence of infection with multiple HPV types was observed in these benign lesions than in the malignant lesions such as high-grade squamous intraepithelial lesions (HSIL) and invasive cervical (ICCA). HPV 16, 18, 31, 33, 51, 52, 56, and 58 were detected as a single infection in HSIL and ICCA, suggesting these are high-risk types for cancer. HPV51, 52 and 58 were more prevalent, whereas HPV18, 33 and 56 were less prevalent in Japanese ICCA than that in the USA.We investigated an association between HLA class II types and susceptibility for cervical cancer or the high-risk HPV infection. Women with HLA DR3, 4 were more susceptible to the high-risk HPV infection, and women with HLA DR2, 3, 4, 5 or with DR2-DQw1, DR3-DQw2, DR5-DQw3 haplotypes were susceptible to cervical cancer. Interestingly, women with DR2, 3, 4, 5 showed higher titers of anti-HPV 16 antibodies that in women with the other HLA types. This suggests that up-regulation of Th2 type immuno-response inducing strong humoral immuno-response may occur in these women with DR2, 3, 4, 5. We surmised that those women may have weaker Th1 response that make susceptible to HPV infection and cervical cancer. Immunohistochemical analysis showed no specific expression patterns of both Th1 and Th2-related cytokines in some tissue samples of cervical cancer. It may be important to study much more samples for such cytokine responses to conduct certain conclusions.

我们最近建立了一种用PCR方法检测大多数粘膜HPV类型DNA的系统，称为LCR-E7 PCR方法。使用这种方法，我们测试了临床样本中HPV感染的患病率。在正常、尖锐湿疣和低度鳞状上皮内病变（LSIL）中发现了超过17种HPV类型。在这些良性病变中观察到多种HPV类型感染的发生率高于恶性病变，如高度鳞状上皮内病变（HSIL）和浸润性宫颈（ICCA）。HPV 16、18、31、33、51、52、56和58在HSIL和ICCA中被检测为单一感染，表明这些是癌症的高风险类型。HPV 51、52和58在日本ICCA中的流行率高于美国，而HPV 18、33和56在日本ICCA中的流行率低于美国。HLA-DR 3、4型的妇女更易感染高危型HPV，HLA-DR 2、3、4、5型或DR 2-DQw 1、DR 3-DQw 2、DR 5-DQw 3单倍型的妇女更易患宫颈癌。有趣的是，DR 2、3、4、5的女性显示出比其他HLA类型的女性更高的抗HPV 16抗体滴度。提示DR 2、3、4、5妇女体内Th 2型免疫应答上调，诱导强烈的体液免疫应答。我们推测，这些妇女可能有较弱的Th 1反应，使易感HPV感染和宫颈癌。免疫组化分析显示，在一些宫颈癌组织标本中，Th 1和Th 2相关细胞因子均无特异性表达。重要的是要研究更多的样本，这样的细胞因子反应，以进行某些结论。