Association of antigen-processing machinery and HLA antigen phenotype of melanoma cells with survival in American Joint Committee on Cancer stage III and IV melanoma patients
Association of antigen-processing machinery and HLA antigen phenotype of melanoma cells with survival in American Joint Committee on Cancer stage III and IV melanoma patients
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DOI：
10.1158/0008-5472.can-06-0854
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发表时间：
2006-06-15
期刊：
影响因子：
11.2
通讯作者：
Ferrone, Soldano
中科院分区：
文献类型：
--
作者：
Anichini, Andrea;Mortarini, Roberta;Ferrone, Soldano
由于黑色素瘤细胞中抗原加工机制（APM）组分和HLA I类和II类抗原表达水平的变化预计会影响它们与宿主免疫系统的相互作用，因此我们评估了这些分子在黑色素瘤病变中表达的定量变化的临床相关性。从85名美国癌症联合委员会（AJCC）III期和IV期患者分离的短期（< 10次体外传代）黑素瘤细胞系用APM组分和HLA I类抗原特异性和HLA II类抗原特异性单克隆抗体染色，并通过流式细胞术分析。所有肿瘤的表型的特征在于肿瘤间和肿瘤内异质性的所有标志物的表达和显着的相关性属于HLA I类抗原加工和呈递途径的标志物的表达水平。平均荧光强度数据的层次聚类定义了两个主要的肿瘤聚类。相应的患者组在总生存率方面存在显著差异，但在其他相关临床变量（包括AJCC分期和术后接受的治疗）方面无显著差异。考克斯回归分析显示β 2-微球蛋白和HLA II类抗原表达与患者生存率显著相关。这一证据得到了证实的免疫组化分析HLA II类抗原表达的黑色素瘤病变从一个无关的组52 AJCC阶段III和IV患者。这些结果表明，APM组件和HLA表达的AJCC III期和IV期患者的黑色素瘤病变的定量变化可能会影响疾病的临床过程。
Because changes in the expression level of antigen-processing machinery (APM) components and HLA class I and II antigens in melanoma cells are expected to affect their interactions with the immune system of the host, we assessed the clinical relevance of quantitative variations in the expression of these molecules in melanoma lesions. Short-term (< 10 in vitro passages) melanoma cell lines isolated from 85 American joint Committee on Cancer (AJCC) stage III and IV patients were stained with APM component and HLA class I antigen-specific and HLA class II antigen-specific monoclonal antibodies and analyzed by flow cytometry. The phenotype of all tumors was characterized by intertumor and intratumor heterogeneity in the expression of all the markers and by significant correlations in the level of expression of markers belonging to the HLA class I antigen-processing and presentation pathway. Hierarchical clustering of the mean fluorescence intensity data defined two main clusters of tumors. The corresponding groups of patients differed significantly in the overall survival but not in other relevant clinical variables, including AJCC stage and therapy received after surgery. Cox regression analysis showed that beta(2)-microglobulin and HLA class II antigen expression were significantly associated with patients' survival. This evidence was corroborated by the immunohistochemical analysis for HLA class II antigen expression of melanoma lesions from an unrelated group of 52 AJCC stage III and IV patients. These results suggest that quantitative variations in APM component and HLA expression in melanoma lesions from AJCC stage III and IV patients may have an effect on the clinical course of the disease.