Analysis of immunobiologic markers in primary and recurrent glioblastoma.
Analysis of immunobiologic markers in primary and recurrent glioblastoma.
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DOI：
10.1007/s11060-017-2732-1
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发表时间：
2018-04
影响因子：
3.9
通讯作者：
Mitchell D
中科院分区：
文献类型：
--
作者：
Rahman M;Kresak J;Yang C;Huang J;Hiser W;Kubilis P;Mitchell D
胶质母细胞瘤（GBM）产生多种免疫反应，了解免疫微环境可能会导致新的免疫治疗方式。本研究的目的是评价原发性与复发性GBM中具有潜在临床意义的免疫学标志物的表达，并评估这些标志物与GBM分子特征之间的关系。对人GBM样本进行评价，并采用免疫组织化学方法分析多种免疫生物学标志物（CD 3、CD 8、FoxP 3、CD 68、CD 163、PD 1、PDL 1、CTLA 4、CD 70）。使用Aperio软件分析免疫反应性。将肿瘤内强阳性免疫反应性的程度与患者和肿瘤特征（包括年龄、性别、MGMT启动子甲基化状态、ATRX、p53和IDH 1突变状态）进行比较。此外，TCGA数据库用于通过期望最大化（RSEM）使用RNA-seq对GBM中的这些因素进行类似的分析。使用比值比，IDH 1突变的GBM具有统计学显著降低的CD 163和CD 70表达以及降低的PD 1、CTLA 4和Foxp 3的趋势。ATRX突变的GBM表现出统计学显著增加的CD 3免疫反应性，而那些与p53突变被发现有显着增加CTLA 4免疫反应性。MGMT甲基化肿瘤中具有强CD 8和CD 68反应性的可能性显着较小。原发性和复发性GBM之间的任何免疫标志物均无显著差异，各年龄段之间的免疫反应性也无显著变化。TCGA分析证实了与IDH 1突变体、p53突变体和MGMT未甲基化肿瘤的差异免疫特征相关的发现。免疫生物学标志物与肿瘤的分子特征的关联性大于与原发/复发状态或年龄的关联性。
Glioblastoma (GBM) generates a varied immune response and understanding the immune microenvironment may lead to novel immunotherapy treatments modalities. The goal of this study was to evaluate the expression of immunologic markers of potential clinical significance in primary versus recurrent GBM and assess the relationship between these markers and molecular characteristics of GBM. Human GBM samples were evaluated and analyzed with immunohistochemistry for multiple immunobiologic markers (CD3, CD8, FoxP3, CD68, CD163, PD1, PDL1, CTLA4, CD70). Immunoreactivity was analyzed using Aperio software. Degree of strong positive immunoreactivity within the tumor was compared to patient and tumor characteristics including age, gender, MGMT promoter methylation status, and ATRX, p53, and IDH1 mutation status. Additionally, the TCGA database was used to perform similar analysis of these factors in GBM using RNA-seq by expectation-maximization (RSEM). Using odds ratios, IDH1 mutated GBM had statistically significant decreased expression of CD163 and CD70 and a trend for decreased PD1, CTLA4, and Foxp3. ATRX-mutated GBMs exhibited statistically significant increased CD3 immunoreactivity, while those with p53 mutations were found to have significantly increased CTLA4 immunoreactivity. The odds of having strong CD8 and CD68 reactivity was significantly less in MGMT methylated tumors. No significant difference was identified in any immune marker between the primary and recurrent GBM, nor was a significant change in immunoreactivity identified among age intervals. TCGA analysis corroborated findings related to the differential immune profile of IDH1 mutant, p53 mutant, and MGMT unmethylated tumors. Immunobiologic markers have greater association with the molecular characteristics of the tumor than with primary/recurrent status or age.
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国际神经病理学协会 - 哈勒姆神经系统肿瘤分类和分级共识指南。
DOI：
10.1111/bpa.12171
发表时间：
2014-09
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Louis DN;Perry A;Burger P;Ellison DW;Reifenberger G;von Deimling A;Aldape K;Brat D;Collins VP;Eberhart C;Figarella-Branger D;Fuller GN;Giangaspero F;Giannini C;Hawkins C;Kleihues P;Korshunov A;Kros JM;Beatriz Lopes M;Ng HK;Ohgaki H;Paulus W;Pietsch T;Rosenblum M;Rushing E;Soylemezoglu F;Wiestler O;Wesseling P;International Society Of Neuropathology--Haarlem
通讯作者：
International Society Of Neuropathology--Haarlem
影响因子：
3.9
作者：
Weathers, Shiao-Pei;Han, Xiaosi;Liu, Diane D.;Conrad, Charles A.;Gilbert, Mark R.;Loghin, Monica E.;O'Brien, Barbara J.;Penas-Prado, Marta;Puduvalli, Vinay K.;Tremont-Lukats, Ivo;Colen, Rivka R.;Yung, W. K. Alfred;de Groot, John F.
通讯作者：
de Groot, John F.
影响因子：
4.1
作者：
Yang, Isaac;Han, Seunggu J.;Parsa, Andrew T.
通讯作者：
Parsa, Andrew T.
DOI：
10.1126/science.1254257
发表时间：
2014-06-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Patel AP;Tirosh I;Trombetta JJ;Shalek AK;Gillespie SM;Wakimoto H;Cahill DP;Nahed BV;Curry WT;Martuza RL;Louis DN;Rozenblatt-Rosen O;Suvà ML;Regev A;Bernstein BE
通讯作者：
Bernstein BE
影响因子：
3.7
作者：
Conroy S;Kruyt FA;Joseph JV;Balasubramaniyan V;Bhat KP;Wagemakers M;Enting RH;Walenkamp AM;den Dunnen WF
通讯作者：
den Dunnen WF