Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project
Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project
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DOI：
10.1182/blood-2003-07-2365
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发表时间：
2004-06-01
期刊：
影响因子：
20.3
通讯作者：
Grogan, TM
中科院分区：
文献类型：
--
作者：
Rimsza, LM;Roberts, RA;Grogan, TM
白血病和淋巴瘤分子图谱项目最近公布了对240例弥漫性大B细胞淋巴瘤(DLBCL)进行DNA微阵列分析的结果。四个基因表达“信号”被确认与患者预后相关，包括主要组织相容性复合体(MHC)II类基因(例如，与更好的生存相关的人类白细胞抗原-DRA)。我们进一步分析了HLA-DRA对生存期的影响，以及与蛋白状态和肿瘤浸润性淋巴细胞相关的基因表达。HLADRA表达最低10%的患者5年总生存率为24%，10%~25%组为37%，25%~50%组为50%，最高50%组为55%。进一步分析表明，死亡风险比是人类白细胞抗原-DRA表达的非线性函数。对国际预后指数的调整并没有改变人类白细胞抗原-DRA对生存率的影响。其他MHC II类基因也被发现类似地预测生存。在接受评估的22例患者中，有20例的微阵列HLA-DRA表达与人类白细胞抗原-DR(人类白细胞抗原-DR)蛋白的存在与否相关。在MHC II类基因阴性的患者中，检测到的肿瘤浸润性CD8(+)T细胞比阳性患者少(2.8%比11.0%；P=.001)，这支持了肿瘤免疫监视的丧失对DLBCL患者预后具有破坏性影响的假设。(C)2004年，由美国血液病学会提供。
The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA) which correlated with better survival. We further analyzed the effects of HLA-DRA on survival and correlated gene expression with protein status and tumor-infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10% of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group, and 55% for patients in the highest 50%. Further analysis demonstrated that the hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment for the International Prognostic Index did not alter the impact of HLA-DRA on survival. Other MHC class II genes were found to predict survival similarly. Microarray HLA-DRA expression correlated with the presence or absence of human leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor-infiltrating CD8(+) T cells were detected in MHC class II-negative cases compared with positive cases (2.8% versus 11.0%; P = .001), supporting the hypothesis that loss of tumor immunosurveillance has a devastating effect on patient outcome in DLBCL. (C) 2004 by The American Society of Hematology.