LOH in the HLA class I region at 6p21 is associated with shorter survival in newly diagnosed adult glioblastoma.
LOH in the HLA class I region at 6p21 is associated with shorter survival in newly diagnosed adult glioblastoma.
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DOI：
10.1158/1078-0432.ccr-12-2861
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发表时间：
2013-04-01
期刊：
影响因子：
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通讯作者：
Okada H
中科院分区：
文献类型：
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作者：
Yeung JT;Hamilton RL;Ohnishi K;Ikeura M;Potter DM;Nikiforova MN;Ferrone S;Jakacki RI;Pollack IF;Okada H
胶质母细胞瘤（GBM）表现出人类白细胞抗原（HLA）I类的表达下调，从而逃避细胞毒性T细胞并限制免疫疗法的功效。HLA I类（6p 21）和/或β 2微球蛋白（B2 m）（15 q21）区域的洛代表不可逆的下调。在这项研究中，我们研究了这些洛缺失事件的发生率及其与GBM总生存率的关系。在对60例成人GBM患者的横断面分析中，通过PCR以及免疫组化评估HLA I类表达和CD 8 + T细胞浸润，对来自福尔马林固定石蜡包埋标本的DNA进行了HLA I类、B2 m、HLA II类、HLA III类和6 q的10个微卫星区域的评估。HLA I类、B2 m、HLA II类、HLA III类和6 q区域的洛缺失率分别为41.4%、18.2%、9.4%、77.8%和36.0%。HLA I类洛缺失与总生存期缩短相关（HR = 4.89，p = 0.0078）。基于免疫组化，HLA I类在22 - 43%的病例中下调。显示阴性染色的病例明显更年轻。HLA I类表达与肿瘤内CD 8 + T细胞浸润相关。在成人GBM中，HLA I类区域的洛是常见的。该区域的洛缺失与较短的生存期相关，提示这些基因在免疫监视中起着至关重要的作用。
Glioblastoma (GBM) demonstrate down-regulated expression of Human Leukocyte Antigen (HLA) Class I, thereby escaping from cytotoxic T cells and limiting the efficacy of immunotherapy. LOH of HLA Class I (6p21) and/or Beta-2 microglobulin (B2m) (15q21) regions represent irreversible down-regulation. In this study, we examined the prevalence of these LOH events and their relations with overall survival in GBM. In a cross-sectional analysis on 60 adult GBM patients, DNA from formalin-fixed paraffin-embedded specimens were evaluated for ten microsatellite regions of HLA Class I, B2m, HLA Class II, HLA Class III, and 6q by PCR as well as immunohistochemical evaluation of HLA Class I expression and CD8+ T cell infiltration. LOH in HLA Class I, B2m, HLA Class II, HLA Class III, and 6q regions were present in 41.4%, 18.2%, 9.4%, 77.8%, and 36.0% of informative cases, respectively. LOH of HLA Class I was associated with shorter overall survival (HR = 4.89, p = 0.0078). HLA Class I was down-regulated in 22 to 43% of cases based on immunohistochemistry. Cases that displayed negative staining were significantly younger. HLA Class I expression correlated with intratumoral CD8+ T cell infiltration. LOH in the HLA Class I region is frequent in adult GBMs. The association of shorter survival with LOH in this region suggest a crucial role for these genes in immunosurveillance.