Genome Medicine (May 2019)
Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data
- 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. Estrada,
- Paula Ericsson-Gonzalez,
- Pornpimol Charoentong,
- Justin Balko,
- Noel Filipe da Cunha Carvalho de Miranda,
- Zlatko Trajanoski
Affiliations
- Francesca Finotello
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Clemens Mayer
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Christina Plattner
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Gerhard Laschober
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Dietmar Rieder
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Hubert Hackl
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Anne Krogsdam
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Zuzana Loncova
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- Wilfried Posch
- Division of Hygiene and Medical Microbiology, Medical University of Innsbruck
- Doris Wilflingseder
- Division of Hygiene and Medical Microbiology, Medical University of Innsbruck
- Sieghart Sopper
- Department of Haematology and Oncology, Medical University of Innsbruck
- Marieke Ijsselsteijn
- Department of Pathology, Leiden University Medical Centre
- Thomas P. Brouwer
- Department of Pathology, Leiden University Medical Centre
- Douglas Johnson
- Vanderbilt University
- Yaomin Xu
- Department of Biostatistics, Vanderbilt University Medical Center
- Yu Wang
- Department of Biostatistics, Vanderbilt University Medical Center
- Melinda E. Sanders
- Department Pathology Microbiology and Immunology, Vanderbilt University Medical Center
- Monica V. Estrada
- Department Pathology Microbiology and Immunology, Vanderbilt University Medical Center
- Paula Ericsson-Gonzalez
- Department Pathology Microbiology and Immunology, Vanderbilt University Medical Center
- Pornpimol Charoentong
- Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg
- Justin Balko
- Vanderbilt University
- Noel Filipe da Cunha Carvalho de Miranda
- Department of Pathology, Leiden University Medical Centre
- Zlatko Trajanoski
- Biocenter, Division of Bioinformatics, Medical University of Innsbruck
- DOI
- https://doi.org/10.1186/s13073-019-0638-6
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 20
Abstract
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.
Keywords
