Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors
Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors
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DOI：
10.1158/1078-0432.ccr-04-2588
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发表时间：
2005-12-01
影响因子：
11.5
通讯作者：
Ferrone, S
中科院分区：
文献类型：
--
作者：
Facoetti, A;Nano, R;Ferrone, S
目的：探讨人类白细胞抗原(人类白细胞抗原)和抗原处理机制(APM)成分在恶性脑肿瘤中异常表达的发生率。这些信息可能有助于我们理解恶性脑肿瘤使用的免疫逃逸机制，因为HLA抗原介导了肿瘤细胞与宿主免疫系统的相互作用。实验设计：88例手术切除的恶性星形细胞肿瘤，根据WHO标准分类，用识别单态、位点特异性和同种异体决定簇的单抗、位点特异性和同种异体决定簇的单抗、β(2)-微球蛋白、APM成分(LMP2、LMP7、TAP1、TAP2、Calnexin、Calreticin和Tapasin)进行免疫过氧化酶反应。结果：在47个多形性胶质母细胞瘤(GEM)病变中，50%的HLAI类抗原丢失，在18个2级星形细胞瘤病变中，20%的HLAI类抗原染色阳性。在24个基底膜病变中，有80%的病变有选择性的HLA-A2抗原丢失，在12个2级星形细胞瘤病变中，有50%的病变染色。HL A-I类抗原丢失与肿瘤分级显著相关(P<；0.025)。在所研究的APM成分中，Tapasin的表达在所分析的GEM皮损中下调的比例类似于20%；它与HLAI类抗原下调和肿瘤分级相关，尽管不显著。在所分析的44个病灶中，有30%的病灶检测到了人类白细胞抗原11类抗原的表达。结论：人类白细胞抗原缺陷在恶性脑肿瘤中的存在可能解释了迄今为止在大多数以T细胞为基础的免疫治疗临床试验中观察到的相对较差的临床有效率的原因。
Purpose: To determine the frequency of abnormalities in human leukocyte antigen (HLA) and antigen processing machinery (APM) component expression in malignant brain tumors. This information may contribute to our understanding of the immune escape mechanisms used by malignant brain tumors because HLA antigens mediate interactions of tumor cells with the host's immune system.Experimental Design: Eighty-eight surgically removed malignant astrocytic tumors, classified according to the WHO criteria, were stained in immunoperoxidase reactions with monoclonal antibody recognizing monomorphic, locus-specific, and allospecific determinants of HLA class I antigens, beta(2)-microglobulin, APM components (LMP2, LMP7,TAP1,TAP2, calnexin, calreticulin, and tapasin), and HLA class 11 antigens.Results: HLA class I antigens were lost in similar to 50% of the 47 glioblastoma multiforme (GEM) lesions and in similar to 20% of the 18 grade 2 astrocytoma lesions stained. Selective HLA-A2 antigen loss was observed in similar to 80% of the 24 GBM lesions and in similar to 50% of the 12 grade 2 astrocytoma lesions stained. HLA class I antigen loss was significantly (P < 0.025) correlated with tumor grade. Among the APM components investigated, tapasin expression was down-regulated in similar to 20% of the GEM lesions analyzed; it was associated, although not significantly, with HLA class I antigen down-regulation and tumor grade. HLA class 11 antigen expression was detected in similar to 30% of the 44 lesions analyzed.Conclusion: The presence of HLA antigen defects in malignant brain tumors may provide an explanation for the relatively poor clinical response rates observed in the majority of the T cell based immunotherapy clinical trials conducted to date in patients with malignant brain tumors.