Advanced Molecular Characterization Using Digital Spatial Profiling Technology on Immunooncology Targets in Methylated Compared with Unmethylated IDH-Wildtype Glioblastoma.
Advanced Molecular Characterization Using Digital Spatial Profiling Technology on Immunooncology Targets in Methylated Compared with Unmethylated IDH-Wildtype Glioblastoma.
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DOI：
10.1155/2021/8819702
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发表时间：
2021
影响因子：
--
通讯作者：
Kurian KM
中科院分区：
文献类型：
--
作者：
Barber H;Tofias A;Lander B;Daniels A;Gong J;Ren Y;Ren X;Liang Y;White P;Kurian KM
胶质母细胞瘤（GBM）是最常见的原发性成人脑肿瘤，中位总生存期（OS）为12-15个月。GBM中多个免疫肿瘤学靶点的分子特征可能有助于靶向新的免疫治疗策略。我们使用NanoString GeoMx®数字空间轮廓（DSP）来评估甲基化与非甲基化IDH-野生型胶质母细胞瘤中的多种免疫肿瘤学蛋白靶点。 NanoString GeoMx® DSP技术使用多个一抗与具有UV光可切割接头的索引DNA寡核苷酸缀合。用结合的荧光抗体选择感兴趣的组织区域（ROI）;通过UV介导的接头释放寡核苷酸并定量。我们使用DSP多重分析31种免疫肿瘤蛋白和对照（CD 4、CD 14、CD 68、CD 8A、B7-H3、PD-L1、CD 19、FOXP 3、CD 44、STAT 3（磷酸Y 705）、CD 45、泛细胞角蛋白、MS 4A 1/CD 20、CD 45 RO、PD 1、CD 3、β-2微球蛋白、VISTA、Bcl 2、GZMB、PTEN、β-连环蛋白、CD 56、Ki-67、STAT 3、AKT、p-Akt、S6、组蛋白H3、IgG兔对照和小鼠IgG对照）。nCounter平台允许MGMT甲基化和未甲基化肿瘤中ROI之间的抗体定量比较。使用技术和生物学重复比较甲基化和未甲基化GBM之间的平均蛋白质表达计数。 分析显示，10/27种免疫肿瘤学靶蛋白在甲基化相对于未甲基化的IDH-野生型胶质母细胞瘤肿瘤核心中显著增加（通过Benjamini-Hochberg程序，错误发现率（FDR）<0.1）。 NanoString GeoMx® DSP用于分析甲基化与未甲基化的IDH野生型胶质母细胞瘤中的多种免疫肿瘤学蛋白靶表达。在这项小型研究中，甲基化与非甲基化GBM肿瘤核心中的CD 4、CD 14、CD 68、CD 8A、B7-H3、PDL-1、CD 19、FOXP 3、CD 44和STAT 3蛋白表达在统计学上增加;然而，这需要更大的队列验证。先进的多重免疫肿瘤学生物标志物分析可能有助于识别GBM中新型免疫抑制剂的生物标志物。
Glioblastoma (GBM) is the most common primary adult brain tumour with a median overall survival (OS) of 12–15 months. Molecular characterization of multiple immunooncology targets in GBM may help target novel immunotherapeutic strategies. We used NanoString GeoMx® Digital Spatial Profiling (DSP) to assess multiple immunooncology protein targets in methylated versus unmethylated IDH-wild-type glioblastoma. NanoString GeoMx® DSP technology uses multiple primary antibodies conjugated to indexing DNA oligos with a UV photocleavable linker. Tissue regions of interest (ROIs) are selected with bound fluorescent antibodies; oligos are released via a UV-mediated linker and quantitated. We used DSP multiplex analysis of 31 immunooncology proteins and controls (CD4, CD14, CD68, CD8A, B7-H3, PD-L1, CD19, FOXP3, CD44, STAT3 (phospho Y705), CD45, Pan Cytokeratin, MS4A1/CD20, CD45RO, PD1, CD3, beta-2 microglobulin, VISTA, Bcl2, GZMB, PTEN, beta-catenin, CD56, Ki-67, STAT3, AKT, p-Akt, S6, Histone H3, IgG Rabbit control, and Mouse IgG control) from ROIs in a cohort of 10 IDH-wild-type glioblastomas (5 methylated and 5 unmethylated). An nCounter platform allowed quantitative comparisons of antibodies between ROIs in MGMT methylated and unmethylated tumours. Mean protein expression counts between methylated and unmethylated GBM were compared using technical and biological replicates. The analysis showed 10/27 immunooncology target proteins were significantly increased in methylated versus unmethylated IDH-wild-type glioblastoma tumour core (false discovery rate (FDR) <0.1 by Benjamini–Hochberg procedure). NanoString GeoMx® DSP was used to analyse multiple immunooncology protein target expression in methylated versus unmethylated IDH-wild-type glioblastoma. In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.
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影响因子：
11.2
作者：
Le Mercier I;Chen W;Lines JL;Day M;Li J;Sergent P;Noelle RJ;Wang L
通讯作者：
Wang L
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
12.7
作者：
ROSSI, ML;HUGHES, JT;BROWNELL, DB
通讯作者：
BROWNELL, DB
影响因子：
11.2
作者：
Fecci, PE;Mitchell, DA;Sampson, JH
通讯作者：
Sampson, JH
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators