Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer.
Association of HLA class I antigen abnormalities with disease progression and early recurrence in prostate cancer.
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DOI：
10.1007/s00262-009-0769-5
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Hartmann A
中科院分区：
文献类型：
--
作者：
Seliger B;Stoehr R;Handke D;Mueller A;Ferrone S;Wullich B;Tannapfel A;Hofstaedter F;Hartmann A
HLA I类抗原加工机制（APM）组分表达的缺陷通常对肿瘤的临床过程和对基于T细胞的免疫疗法的应答具有负面影响。由于只有很少的信息是可用的频率和临床意义的HLA I类APM组件异常的前列腺癌，APM组件的表达模式进行了分析，在59个原发性前列腺癌，邻近的正常组织，以及在前列腺癌细胞系。IFN-γ诱导的蛋白酶体亚基LMP 2和LMP 7、TAP 1、TAP 2、钙连接蛋白、钙网蛋白、ERp 57和tapasin在正常前列腺细胞的细胞质中强烈表达，而HLA I类重链（HC）和β2-微球蛋白在细胞表面上表达。大多数APM组分在相当数量的前列腺癌中下调。除了在约0.5%的肿瘤病变中未检测到HLA I类HC、TAP 2和ERp 57外，在至少21%的分析病变中未检测到所有其他APM组分。这些APM成分缺陷与较高的肿瘤Gleason分级和早期疾病复发相关。前列腺癌细胞系也表现出异质性，但减少的组成型APM组分表达模式与缺乏或减少的HLA I类表面抗原相关，其可以被IFN-γ上调。我们的研究结果表明，HLA I类APM组分异常主要是由于调节机制，在前列腺癌的临床过程中发挥作用，并对基于T细胞的免疫治疗的结果。
Defects in HLA class I antigen processing machinery (APM) component expression often have a negative impact on the clinical course of tumors and on the response to T cell-based immunotherapy. Since only scant information is available about the frequency and clinical significance of HLA class I APM component abnormalities in prostate cancer, the APM component expression pattern was analyzed in 59 primary prostate carcinoma, adjacent normal tissues, as well as in prostate carcinoma cell lines. The IFN-γ inducible proteasome subunits LMP2 and LMP7, TAP1, TAP2, calnexin, calreticulin, ERp57, and tapasin are strongly expressed in the cytoplasm of normal prostate cells, whereas HLA class I heavy chain (HC) and β2-microglobulin are expressed on the cell surface. Most of the APM components were downregulated in a substantial number of prostate cancers. With the exception of HLA class I HC, TAP2 and ERp57 not detectable in about 0.5% of tumor lesions, all other APM components were not detected in at least 21% of lesions analyzed. These APM component defects were associated with a higher Gleason grade of tumors and an early disease recurrence. Prostate carcinoma cell lines also exhibit a heterogeneous, but reduced constitutive APM component expression pattern associated with lack or reduced HLA class I surface antigens, which could be upregulated by IFN-γ. Our results suggest that HLA class I APM component abnormalities are mainly due to regulatory mechanisms, play a role in the clinical course of prostate cancer and on the outcome of T cell-based immunotherapies.
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影响因子：
11.2
作者：
Norell, Hakan;Carlsten, Mattias;Kiessling, Rolf
通讯作者：
Kiessling, Rolf
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。
影响因子：
5.8
作者：
Mehta, Akash M.;Jordanova, Ekaterina S.;Kenter, Gemma G.;Ferrone, Soldano;Fleuren, Gert-Jan
通讯作者：
Fleuren, Gert-Jan
影响因子：
11.5
作者：
Meissner, M;Reichert, TE;Seliger, B
通讯作者：
Seliger, B
影响因子：
3.8
作者：
Leys, Charles M.;Nomura, Sachiyo;Goldenring, James R.
通讯作者：
Goldenring, James R.
影响因子：
6.4
作者：
Kasper, G;Weiser, AA;Lehmann, K
通讯作者：
Lehmann, K