A fundamental study about the new therapeutic stratedy with cell mediated immunity sysytem for uterine cervical cancer and CIN

细胞免疫系统治疗宫颈癌及CIN新策略的基础研究

• 批准号: 17591716
• 负责人: OKI Akinori
• 金额: $ 2.24万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591716/
• 关键词: HPV; HLA; cervical cancer; immunotherapy; 子宮頸癌; CIN

As a result of multi-institutions collaborative investigation intended to elucidate the natural history by observating CIN1/2, it developed that there were two steps by the process during carcinogenesis of CIN1/2. The study subjects consisted of 570 women aged 54 or younger with cytologically and histologically confirmed CIN 1/2. CIN cases included 479 CIN 1 and 91 CIN 2. The median follow-up time was 38.1 months. The 570 subjects were divided into 361 (63.3%) patients with regression, 172 (28.6%) patients with persistence and 46 (8.1%) patients with progression. The median regression time was 6.5 months and the median progression time was 17.9 months, suggesting that regression is an early event and progression is a late event in the national history of CIN 1/2. Thus, the first step is a step to persist without regression of the CIN1/2 within two years usually disappearing. The second step is the step that persisted CIN1/2 which continued progresses to CIN3. We used hazard ratio after … More adjustment of Age, CIN grade and HPV category to evaluate various prognostic factors, because the three factors were closely associated with both regression and progression in the univariate analysis. Age, CIN grade, HPV risk category, smoking, marital status, and number of sexual partners were significantly associated with CIN persistence, whereas CIN grade, HPV risk category and HLA class II allele (HLA DRB1*1302) had significant association with CIN progression.In such a background we paid attention to the type of HPV and the haplotype of the HLA Class I antigen in elements of the uterine cervix cancer.It is obvious that high-risk HPV infection is a direct trigger in the carcinogenesis of uterine cervix cancer, but evasion from virus immunity and tumor immunity by the host is indispensable in carcinogenesis process. These immune mechanism due to cell-mediated immunity through the T lymphocyte, and co-existence of HLA class I molecules and the HPV specific peptide is important for this system. The complex of HLA class I molecules with peptide consisting of around 9-10 amino acids, is recognized as an antigen by a T lymphocytes. The binding affinity of the peptide is HLA type specific, so that the immune response depends on the difference of the HLA haplotypes.13 kinds of cell lines, which were derived from cervical cancer, were analysed both HPV and HLA typings. HPV16 was detected by seven lines of those, and HPV18 was detected by three, and it was not detected from one. Three of seven HPV16 positive lines were positive for A*1101 and five of these positive for A*2401, but did not accumulate the HLA of seven HPV16 positive lines in a specific haplotype in B, C locus. The distribution in which locus did not have regional control and significant difference. About half in HLA A, B locus and about two-thirds in C locus were coverd by these seven HPV16 positive cell lines, A susceptibility of the cervical cancer by the difference of the HLA might be identified in future by comparing the HLA distribution of the uterine cervix cancer patient of the specific HPV (especially HPV16) positive with normal regional control. Less

多机构合作研究的结果是通过观察CIN 1/2来阐明其自然史，发现CIN 1/2的癌变过程分为两个步骤。研究对象包括570名年龄在54岁或以下的女性，经细胞学和组织学证实为CIN 1/2。CIN 1型479例，CIN 2型91例。中位随访时间为38.1个月。570例受试者分为361例（63.3%）消退患者、172例（28.6%）持续患者和46例（8.1%）进展患者。中位消退时间为6.5个月，中位进展时间为17.9个月，表明在CIN 1/2的国家历史中，消退是早期事件，进展是晚期事件。因此，第一步是坚持两年内CIN 1/2不消退的步骤，通常会消失。第二步是持续CIN 1/2的步骤，继续进展到CIN 3。我们使用风险比， ...更多信息 调整年龄、CIN分级和HPV类型以评估各种预后因素，因为这三个因素在单因素分析中与消退和进展密切相关。年龄、CIN分级、HPV风险类别、吸烟、婚姻状况和性伴侣数量与CIN持续性显著相关，而CIN分级、HPV危险类型和HLA II类等位基因（HLA DRB 1 *1302）在此背景下，我们将注意力集中在宫颈癌分子中HPV的类型和HLA-I类抗原的单倍型上，显然，高危型HPV感染是宫颈癌发生的直接触发因素，但宿主对病毒免疫和肿瘤免疫的逃避是癌变过程中不可或缺的。这些免疫机制是由于T淋巴细胞介导的细胞免疫，以及HLA I类分子和HPV特异性肽的共存对该系统至关重要。HLA I类分子与由约9-10个氨基酸组成的肽的复合物被T淋巴细胞识别为抗原。肽的结合亲和力是HLA型特异性的，因此免疫应答取决于HLA单倍型的差异。13种细胞系，这是来自宫颈癌，分析了HPV和HLA分型。其中7株检测到HPV 16，3株检测到HPV 18，1株未检测到。7株HPV 16阳性细胞系中3株A*1101阳性，5株A*2401阳性，但在B、C位点上未聚集7株HPV 16阳性细胞系的HLA。其中位点分布不存在地区控制和显著差异。这7株HPV 16阳性细胞系的HLA A、B位点约占一半，C位点约占2/3。通过比较特异性HPV（尤其是HPV 16）阳性的宫颈癌患者与正常地区对照的HLA分布，可进一步确定宫颈癌的易感性。少

项目成果

HPV感染と危険因子

HPV 感染和危险因素

• 发表时间: 2006
• 期刊: 産婦人科治療 93・6
• 作者: 沖明典;吉川裕之
• 通讯作者: 吉川裕之

コホート研究に基づくCIN1/2の管理方針と高危険部の抽出

基于队列研究的CIN1/2管理政策及高危区域提取

• 发表时间: 2006
• 期刊: 日本産婦人科学会誌 58巻・11号
• 作者: K.Matsumoto;T.Yasugi;A.Oki;T.Fujii;C.Negate;S.Sekiya;H.Hoshiai;Y.Taketani;T.Kanda;T.Kawana;H.Yoshikawa;沖 明典;沖 明典
• 通讯作者: 沖 明典

Identification of high-risk CIN 1/2 and its management based on a large scale cohort study of CIN 1/2 in Japan

基于日本CIN 1/2大规模队列研究的高危CIN 1/2识别及其管理

• 发表时间: 2006
• 期刊: Nippin Sanka-Hujinnka-gakkai zasshi Vol.58(11)
• 作者: Takeuchi T;Tsutsumi O;Ikezuki Y;Kamei Y;Osuga Y;Fujiwara T;Takai Y;Momoeda M;Yano T;Taketani Y.;A.Oki
• 通讯作者: A.Oki

子宮頸癌のスクリーニング

宫颈癌筛查

• 发表时间: 2006
• 期刊: 産婦人科の実際 55巻・11号
• 作者: K.Matsumoto;T.Yasugi;A.Oki;T.Fujii;C.Negate;S.Sekiya;H.Hoshiai;Y.Taketani;T.Kanda;T.Kawana;H.Yoshikawa;沖 明典
• 通讯作者: 沖 明典

IgG antibodies to HPV16, 52, 58 and 6 L1-capsids and spontaneous regression of cervical intraepithelial neoplasia

HPV16、52、58 和 6 L1 衣壳的 IgG 抗体与宫颈上皮内瘤变的自然消退

• 发表时间: 2006
• 期刊: Cancer Letters Vol.231(peer reviewed)
• 作者: K. Matsumoto;T. Yasugi;A. Oki;T. Fujii;C. Nagata;S. Sekiya;H. Hoshiai;Y. Taketani;T. Kanda;T. Kawana;H. Yoshikawa
• 通讯作者: H. Yoshikawa