Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma.
Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma.
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抗原加工机械和HLA I类缺陷与宫颈癌中临床病理结果的关联。
DOI：
10.1007/s00262-007-0362-8
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发表时间：
2008-02
影响因子：
5.8
通讯作者：
Fleuren, Gert-Jan
中科院分区：
文献类型：
--
作者：
Mehta, Akash M.;Jordanova, Ekaterina S.;Kenter, Gemma G.;Ferrone, Soldano;Fleuren, Gert-Jan
HLA I类缺失是宫颈癌免疫逃避的重要机制，影响了免疫疗法和癌症疫苗的发展。我们报告了HLA I类和抗原加工机械成分表达及其与临床结果的关联的系统调查。采用组织芯片对109例宫颈癌患者的癌灶进行HLA I类重链、β2-微球蛋白、LMP2、LMP7、LMP10、TAP1、TAP2、ERAP1、tapasin、钙网蛋白、calreticulin、calnexin和ERp57的染色。采用一种新的染色评估方法，以确保表达数据的最佳准确性和可靠性，这些数据与已知的临床病理参数相关。HLA I类部分缺失与5年总生存率降低显著相关（正常表达组为61%，正常表达组为83%，P < 0.05），与5年无病生存率（DFS）降低相关（正常表达组为65%，正常表达组为82%，P = 0.05）。除LMP10、calnexin和calreticulin外，在大量病例中，所有APM成分均下调，除ERAP1外，与HLA I类下调显著相关。LMP7、TAP1和ERAP1缺失与总体DFS和DFS （LMP7除外）降低显著相关（P分别< 0.05和0.005）。多因素分析中，ERAP1下调是总体和DFS变差的独立预测因子（HR分别为3.08,P < 0.05和2.84,P < 0.05）。HLA I类和APM成分下调在宫颈癌中经常发生，而ERAP1缺失导致的肽库改变是导致肿瘤进展和死亡的主要因素。
HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β2-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P < 0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P = 0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P < 0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P < 0.05 and HR 2.84; P < 0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality.
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影响因子：
4.4
作者：
Perosa, F;Luccarelli, G;Dammacco, F
通讯作者：
Dammacco, F
影响因子：
--
作者：
Ogino, T;Wang, X;Ferrone, S
通讯作者：
Ferrone, S
影响因子：
11.5
作者：
Meissner, M;Reichert, TE;Seliger, B
通讯作者：
Seliger, B
影响因子：
4.7
作者：
Cao, BW;Tian, XY;Ke, Y
通讯作者：
Ke, Y
影响因子：
4.4
作者：
Barnden, MJ;Purcell, AW;McCluskey, J
通讯作者：
McCluskey, J