Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data

通过 RNA 测序数据反卷积揭示肿瘤免疫结构的分子和药理调节剂

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作者:Francesca Finotello, Clemens Mayer, Christina Plattner, Gerhard Laschober, Dietmar Rieder, Hubert Hackl, Anne Krogsdam, Zuzana Loncova, Wilfried Posch, Doris Wilflingseder, Sieghart Sopper, Marieke Ijsselsteijn, Thomas P Brouwer, Douglas Johnson, Yaomin Xu, Yu Wang, Melinda E Sanders, Monica V Estra

Abstract

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 .

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