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

by Brouwer, Thomas P. , de Miranda, Noel Filipe da Cunha Carvalho , Wang, Yu , Wilflingseder, Doris , Finotello, Francesca , Ijsselsteijn, Marieke , Mayer, Clemens , Balko, Justin , Laschober, Gerhard , Johnson, Douglas , Charoentong, Pornpimol , Hackl, Hubert , Krogsdam, Anne , Loncova, Zuzana , Estrada, Monica V. , Rieder, Dietmar , Plattner, Christina , Xu, Yaomin , Sopper, Sieghart , Sanders, Melinda E. , Ericsson-Gonzalez, Paula , Posch, Wilfried , Trajanoski, Zlatko

in Algorithms / Antibodies / B cells / Bioinformatics / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer immunology / Cancer Research / Care and treatment / Cell activation / Cell Line, Tumor / Colorectal cancer / CXCR3 protein / Cytotoxicity / Datasets / Deconvolution / Flow cytometry / Gene expression / Gene Expression Profiling - methods / Genomics / Human Genetics / Humans / Immune contexture / Immunohistochemistry / Immunomodulation / Immunotherapy / Immunotherapy - methods / Kinases / Lymphocytes / Lymphocytes T / Medical research / Medicine/Public Health / Metabolomics / Metastases / Method / Neoplasms - genetics / Neoplasms - immunology / Neoplasms - therapy / Prognosis / Ribonucleic acid / RNA / RNA-seq / Sequence Analysis, RNA - methods / Systems Biology / T cells / Tumor immune microenvironment and immunotherapy / Tumors

2019

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

2019

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

2019

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Journal Article

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

Brouwer, Thomas P.,

de Miranda, Noel Filipe da Cunha Carvalho,

Wang, Yu,

Wilflingseder, Doris,

Finotello, Francesca,

Ijsselsteijn, Marieke,

Mayer, Clemens,

Balko, Justin,

Laschober, Gerhard,

Johnson, Douglas,

Charoentong, Pornpimol,

Hackl, Hubert,

Krogsdam, Anne,

Loncova, Zuzana,

Estrada, Monica V.,

Rieder, Dietmar,

Plattner, Christina,

Xu, Yaomin,

Sopper, Sieghart,

Sanders, Melinda E.,

Ericsson-Gonzalez, Paula,

Posch, Wilfried,

Trajanoski, Zlatko

2019

Overview

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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Publisher

BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC

Subject

/ B cells

/ Biomedical and Life Sciences

/ Biomedicine