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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Genome Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13073-019-0638-6 |
| _version_ | 1819258809068027904 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Francesca Finotello |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T19:00:01Z |
| format | Article |
| id | doaj.art-efe12b1b010b4124877e3449d722878c |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-12-23T19:00:01Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-efe12b1b010b4124877e3449d722878c2022-12-21T17:34:44ZengBMCGenome Medicine1756-994X2019-05-0111112010.1186/s13073-019-0638-6Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq dataFrancesca Finotello0Clemens Mayer1Christina Plattner2Gerhard Laschober3Dietmar Rieder4Hubert Hackl5Anne Krogsdam6Zuzana Loncova7Wilfried Posch8Doris Wilflingseder9Sieghart Sopper10Marieke Ijsselsteijn11Thomas P. Brouwer12Douglas Johnson13Yaomin Xu14Yu Wang15Melinda E. Sanders16Monica V. Estrada17Paula Ericsson-Gonzalez18Pornpimol Charoentong19Justin Balko20Noel Filipe da Cunha Carvalho de Miranda21Zlatko Trajanoski22Biocenter, Division of Bioinformatics, Medical University of InnsbruckBiocenter, Division of Bioinformatics, Medical University of InnsbruckBiocenter, Division of Bioinformatics, Medical University of InnsbruckBiocenter, Division of Bioinformatics, Medical University of InnsbruckBiocenter, Division of Bioinformatics, Medical University of InnsbruckBiocenter, Division of Bioinformatics, Medical University of InnsbruckBiocenter, Division of Bioinformatics, Medical University of InnsbruckBiocenter, Division of Bioinformatics, Medical University of InnsbruckDivision of Hygiene and Medical Microbiology, Medical University of InnsbruckDivision of Hygiene and Medical Microbiology, Medical University of InnsbruckDepartment of Haematology and Oncology, Medical University of InnsbruckDepartment of Pathology, Leiden University Medical CentreDepartment of Pathology, Leiden University Medical CentreVanderbilt UniversityDepartment of Biostatistics, Vanderbilt University Medical CenterDepartment of Biostatistics, Vanderbilt University Medical CenterDepartment Pathology Microbiology and Immunology, Vanderbilt University Medical CenterDepartment Pathology Microbiology and Immunology, Vanderbilt University Medical CenterDepartment Pathology Microbiology and Immunology, Vanderbilt University Medical CenterDepartment of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital HeidelbergVanderbilt UniversityDepartment of Pathology, Leiden University Medical CentreBiocenter, Division of Bioinformatics, Medical University of InnsbruckAbstract 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.http://link.springer.com/article/10.1186/s13073-019-0638-6Cancer immunologyImmunotherapyDeconvolutionRNA-seqImmune contexture |
| spellingShingle | 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 Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data Genome Medicine Cancer immunology Immunotherapy Deconvolution RNA-seq Immune contexture |
| title | Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data |
| title_full | Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data |
| title_fullStr | Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data |
| title_full_unstemmed | Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data |
| title_short | Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data |
| title_sort | molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of rna seq data |
| topic | Cancer immunology Immunotherapy Deconvolution RNA-seq Immune contexture |
| url | http://link.springer.com/article/10.1186/s13073-019-0638-6 |
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