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Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data.
Genome Medicine ( IF 12.3 ) Pub Date : 2019-05-24 , DOI: 10.1186/s13073-019-0638-6
Francesca Finotello 1 , Clemens Mayer 1 , Christina Plattner 1 , Gerhard Laschober 1 , Dietmar Rieder 1 , Hubert Hackl 1 , Anne Krogsdam 1 , Zuzana Loncova 1 , Wilfried Posch 2 , Doris Wilflingseder 2 , Sieghart Sopper 3 , Marieke Ijsselsteijn 4 , Thomas P Brouwer 4 , Douglas Johnson 5, 6 , Yaomin Xu 7 , Yu Wang 7 , Melinda E Sanders 8 , Monica V Estrada 8 , Paula Ericsson-Gonzalez 8 , Pornpimol Charoentong 9, 10 , Justin Balko 5, 6 , Noel Filipe da Cunha Carvalho de Miranda 4 , Zlatko Trajanoski 1, 11
Affiliation  

We introduce quanTIseq, a method to quantify the fractions of ten immune cell types from bulk RNA-sequencing data. quanTIseq was extensively validated in blood and tumor samples using simulated, flow cytometry, and immunohistochemistry data.quanTIseq analysis of 8000 tumor samples revealed that cytotoxic T cell infiltration is more strongly associated with the activation of the CXCR3/CXCL9 axis than with mutational load and that deconvolution-based cell scores have prognostic value in several solid cancers. Finally, we used quanTIseq to show how kinase inhibitors modulate the immune contexture and to reveal immune-cell types that underlie differential patients' responses to checkpoint blockers.Availability: quanTIseq is available at http://icbi.at/quantiseq .

中文翻译:

通过 RNA-seq 数据的反卷积揭示肿瘤免疫环境的分子和药理学调节剂。

我们引入了 quanTIseq,一种从大量 RNA 测序数据中量化 10 种免疫细胞类型的分数的方法。使用模拟、流式细胞术和免疫组织化学数据在血液和肿瘤样本中对 quanTIseq 进行了广泛验证。对 8000 个肿瘤样本的 quanTIseq 分析表明,与突变负荷相比,细胞毒性 T 细胞浸润与 CXCR3/CXCL9 轴激活的相关性更强,并且基于反卷积的细胞评分对几种实体癌具有预后价值。最后,我们使用 quanTIseq 来展示激酶抑制剂如何调节免疫环境,并揭示导致患者对检查点阻断剂反应不同的免疫细胞类型。可用性:quanTIseq 可从 http://icbi.at/quantiseq 获取。
更新日期:2019-05-24
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