Mechanisms of escape from trastuzumab-mediated ADCC in esophageal squamous cell carcinoma.

食管鳞状细胞癌中曲妥珠单抗介导的 ADCC 的逃逸机制。

• 批准号: 22791268
• 负责人: KAWAGUCHI Yoshihiko
• 金额: $ 2.5万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791268/
• 关键词: 食道扁平上皮癌; 抗体療法; trastuzumab; Herceptin; 細胞障害活性; 抗体依存性細胞障害; ADCC; perforin; granzyme

We elucidated the mechanisms of escape from Trastuzumab-mediated ADCC using esophageal squamous cell carcinoma cell clones. Esophageal SCC cell line TE4, which is highly susceptible to Trastuzumab-mediated ADCC, were repeatedly treated with Trastuzumab-mediated ADCC, and the surviving tumor cells are cloned by limited dilution and selected as 68 escaped tumor clones. Furthermore, the degree of permeabilization induced by PFN and apoptosis induced by the combination of PFN with GrB in tumor cell clones was analyzed. As a result, lower sensitivity for PFN/GrB on tumor clones was related to the reduced Trastuzumab-mediated ADCC. In conclusion, lower susceptibility to the perforin-granzyme system is one of the important mechanisms explaining escape from Trastuzumab-mediated ADCC.

我们使用食管鳞状细胞癌细胞克隆阐明了逃避曲妥珠单抗介导的ADCC的机制。对曲妥珠单抗介导的ADCC高度敏感的食管SCC细胞系TE 4用曲妥珠单抗介导的ADCC重复处理，并且通过有限稀释克隆存活的肿瘤细胞，并选择为68个逃逸的肿瘤克隆。此外，分析PFN诱导的透化程度和PFN与GrB组合诱导的肿瘤细胞克隆的凋亡。因此，PFN/GrB对肿瘤克隆的较低敏感性与曲妥珠单抗介导的ADCC降低有关。总之，对穿孔素-颗粒酶系统的敏感性降低是解释曲妥珠单抗介导的ADCC逃逸的重要机制之一。

项目成果

Inverse correlation of HER2 with MHC class I expression on oesophageal squamous cell carcinoma.

• DOI: 10.1038/sj.bjc.6605772
• 发表时间: 2010-08-10
• 期刊: British journal of cancer
• 影响因子: 8.8

Lapatinib enhances herceptin-mediated antibody-dependent cellular cytotoxicity by up-regulation of cell surface HER2 expression.

• 发表时间: 2011-09
• 期刊: Anticancer research
• 影响因子: 2
• 作者: T. Maruyama;K. Mimura;S. Izawa;A. Inoue;Shugo Shiba;Mitsuaki Watanabe;Y. Kawaguchi;M. Inoue;H. Nogata;S. Inoue;H. Fujii;K. Kono

Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma.

• DOI: 10.1038/sj.bjc.6605502
• 发表时间: 2010-02-02
• 期刊: British journal of cancer
• 影响因子: 8.8

Distribution of Th17 cells and FoxP3(+)regulatory T cells in tumor-infiltrating I ymphocytes, tumor-draining lymph nodes and peripheral blood lymphocytes in patients with gastric cancer.

胃癌患者肿瘤浸润淋巴细胞、肿瘤引流淋巴结及外周血淋巴细胞中Th17细胞和FoxP3(+)调节性T细胞的分布

• 发表时间: 2010
• 期刊: Cancer Sci
• 影响因子: 5.7
• 作者: Kurebayashi J;Moriya T;et al.;Takanori Maruyama
• 通讯作者: Takanori Maruyama

食道扁平上皮癌における HER2を標的とした分子標的治療と免疫治療について

食管鳞癌的分子靶向治疗和针对HER2的免疫治疗

• 发表时间: 2011
• 作者: Takehiko Yokobori;Ryo Takahashi;Yuji Kumakura;Hiroaki Honjo;Keigo Hara;Makoto Sakai;Makoto Sohda;Tatsuya Miyazaki;Takayuki Asao;Hiroyuki Kuwano;Yoshihiro Takemoto;河野浩二;三村耕作
• 通讯作者: 三村耕作