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

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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Affiliated Institutions

• Innsbruck Medical University AT
• Vanderbilt University US
• National Center for Tumor Diseases DE
• University Hospital Heidelberg DE
• Leiden University NL
• Austrian Drug Screening Institute (Austria) AT
• Vanderbilt University Medical Center US
• Heidelberg University DE
• Universität Innsbruck AT

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