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

doi:10.1186/s13073-019-0638-6

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

Genome Med. 2019 May 24;11(1):34. doi: 10.1186/s13073-019-0638-6.

Authors

Francesca Finotello¹, Clemens Mayer¹, Christina Plattner¹, Gerhard Laschober¹, Dietmar Rieder¹, Hubert Hackl¹, Anne Krogsdam¹, Zuzana Loncova¹, Wilfried Posch², Doris Wilflingseder², Sieghart Sopper³, Marieke Ijsselsteijn⁴, Thomas P Brouwer⁴, Douglas Johnson^{5

6}, Yaomin Xu⁷, Yu Wang⁷, Melinda E Sanders⁸, Monica V Estrada⁸, Paula Ericsson-Gonzalez⁸, Pornpimol Charoentong^{9

10}, Justin Balko^{5

6}, Noel Filipe da Cunha Carvalho de Miranda⁴, Zlatko Trajanoski^{11

12}

Affiliations

¹ Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innrain 80, Innsbruck, Austria.
² Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
³ Department of Haematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
⁵ Vanderbilt University, Nashville, TN, USA.
⁶ Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁷ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department Pathology Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁹ Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
¹⁰ Division of Translational Immunotherapy, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹¹ Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innrain 80, Innsbruck, Austria. zlatko.trajanoski@i-med.ac.at.
¹² Austrian Drug Screening Institute, Innrain 66A, Innsbruck, Austria. zlatko.trajanoski@i-med.ac.at.

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: Cancer immunology; Deconvolution; Immune contexture; Immunotherapy; RNA-seq.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Cell Line, Tumor
Gene Expression Profiling / methods*
Humans
Immunotherapy / methods*
Neoplasms / genetics
Neoplasms / immunology*
Neoplasms / therapy
Sequence Analysis, RNA / methods*

Abstract

Publication types

MeSH terms

Grants and funding