Inverse correlation of HER2 with MHC class I expression on oesophageal squamous cell carcinoma.
Inverse correlation of HER2 with MHC class I expression on oesophageal squamous cell carcinoma.
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DOI：
10.1038/sj.bjc.6605772
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发表时间：
2010-08-10
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
由于HER2在30%的食道鳞状细胞癌中表达，以T细胞为基础的免疫治疗和针对HER2的单抗是治疗食管鳞癌的新方法。然而，研究表明，HER2和MHC-I类分子在肿瘤上的表达呈负相关。因此，评估HER2和食管鳞癌MHC-I类表达之间的相关性。采用免疫组织化学、荧光原位杂交(FISH)和流式细胞术检测MHC-I和HER2在80例食管癌组织和细胞系中的表达。我们研究了小干扰RNA(SiRNA)对人食管癌细胞株HER2表达的下调是否能上调MHC-I类分子和抗原提呈机械成分的表达，从而提高其对肿瘤抗原特异性CTL的敏感性。HER2和MHC-I类分子在肿瘤组织和细胞系中的表达呈负相关。通过siRNA下调HER2的表达可上调MHC-I类分子的表达，从而增强肿瘤抗原特异性CTL的识别能力。HER2过表达的ESCC肿瘤细胞通过下调MHC-I类分子对CTL的敏感性降低。
As HER2 is expressed in 30% of oesophageal squamous cell carcinomas (ESCCs), T-cell-based immunotherapy and monoclonal antibodies targeted against HER2 are attractive, novel approaches for ESCCs. However, it was shown that there is an inverse correlation between HER2 and MHC class I expression on tumours. Thus, the correlation between HER2 and MHC class I expressions on ESCC was evaluated. Expressions of MHC class I and HER2 in ESCC tissues (n=80) and cell lines were assessed by immunohistochemistry, fluorescence in situ hybridisation (FISH), and flow cytometry. We investigated whether HER2 downregulation with small interfering RNA (siRNA) in ESCC cell lines could upregulate the expression of MHC class I and the antigen presentation machinery components, and could increase their sensitivity for tumour antigen-specific CTLs. There was an inverse correlation between HER2 and MHC class I expressions in both tumour tissues and cell lines. Downregulation of HER2 with siRNA resulted in the upregulation of MHC class I expression, leading to increased CTL recognition by tumour antigen-specific CTLs. HER2-overexpressing ESCC tumour cells showed a reduced sensitivity for CTLs through the downregulation of MHC class I.
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影响因子：
15.9
作者：
Knutson, KL;Schiffman, K;Disis, ML
通讯作者：
Disis, ML
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11.2
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Herrmann, F;Lehr, HA;Seliger, B
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