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

Francesca Finotello(Innsbruck Medical University), Clemens Mayer(Innsbruck Medical University), Christina Plattner(Innsbruck Medical University), Gerhard Laschober(Innsbruck Medical University), Dietmar Rieder(Innsbruck Medical University), Hubert Hackl(Innsbruck Medical University), Anne Krogsdam(Innsbruck Medical University), Zuzana Loncová(Innsbruck Medical University), Wilfried Posch(Innsbruck Medical University), Doris Wilflingseder(Innsbruck Medical University), Sieghart Sopper(Innsbruck Medical University), Marieke E. Ijsselsteijn(Leiden University), Thomas P. Brouwer(Leiden University), Douglas B. Johnson(Vanderbilt University), Yaomin Xu(Vanderbilt University Medical Center), Yu Wang(Vanderbilt University Medical Center), Melinda E. Sanders(Vanderbilt University Medical Center), Mónica V. Estrada(Vanderbilt University Medical Center), Paula I. González-Ericsson(Vanderbilt University Medical Center), Pornpimol Charoentong(German Cancer Research Center), Justin M. Balko(Vanderbilt University), Noel F.C.C. de Miranda(Leiden University), Zlatko Trajanoski(Innsbruck Medical University)
Genome Medicine
May 24, 2019
Cited by 1,671Open Access
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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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