Defects in the human leukocyte antigen class I antigen-processing machinery in head and neck squamous cell carcinoma: Association with clinical outcome
Defects in the human leukocyte antigen class I antigen-processing machinery in head and neck squamous cell carcinoma: Association with clinical outcome
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DOI：
10.1158/1078-0432.ccr-04-2146
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发表时间：
2005-04-01
影响因子：
11.5
通讯作者：
Seliger, B
中科院分区：
文献类型：
--
作者：
Meissner, M;Reichert, TE;Seliger, B
目的：人类白细胞抗原（HLA）I类抗原缺陷经常存在于头颈部鳞状细胞癌（HNSCC）细胞中，可能为肿瘤提供了逃避免疫监视的机制。关于HNSCC病变和细胞系中HLA I类抗原缺陷的机制，信息很少。在这项研究中，我们研究了抗原加工机制（APM）组分异常在HNSCC细胞产生缺陷型HLA I类表面表达中的作用。使用免疫组织化学、蛋白质印迹和RT-PCR分析，我们将IFN-γ诱导的蛋白酶体亚单位和肽转运蛋白TAP的表达与原发性、复发性、和转移性HNSCC。此外，APM组件和HLA I类抗原的表达在手术切除的病变与疾病的过程中，以评估这些分子的表达缺陷的临床意义。结果：一个高频率的LMP 2，LMP 7，和TAP 1的下调或损失被发现在肿瘤病变和细胞系从HNSCC癌症患者。这些缺陷可以通过将细胞与IFN-γ孵育来纠正。此外，发现原发性HNSCC病变中的LMP 2、LMP 7、TAP 1、TAP 2和HLA I类抗原表达率可预测总生存期。最后，LMP 7的表达水平与疾病复发显着相关，在2 years.Conclusions：我们的研究结果表明，APM组件的表达在HNSCC病变的分析可以提供有用的预后信息与HNSCC患者。
Purpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells.Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-gamma inducible proteasome subunits and of the peptide transporterTAP with that of HLA class I antigens in biopsies and cell lines from primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA class I antigen expression in surgically removed lesions were correlated with the course of the disease in order to assess the clinical significance of deficient expression of these molecules.Results: A high frequency of LMP2, LMP7, and TAP1 down-regulation or loss was found in tumor lesions and cell lines obtained from HNSCC cancer patients. These defects could be corrected by incubating cells with IFN-gamma. Furthermore, LMP2, LMP7,TAP1,TAP2, and HLA class I antigen expression rates in primary HNSCC lesions were found to predict overall survival. Lastly, the level of LMP7 expression was significantly associated with disease recurrence at 2 years.Conclusions: Our results suggest that the analysis of APM component expression in HNSCC lesions can provide useful prognostic information in patients with HNSCC.