Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data

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Cite this article as: eLife 2017;6:e26476 doi: 10.7554/eLife.26476

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Abstract

Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research.

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Author details

Julien Racle

Ludwig Centre for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0100-0323
Kaat de Jonge

Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.
Petra Baumgaertner

Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.
Daniel E Speiser

Department of Fundamental Oncology, Lausanne University Hospital, Epalinges, Switzerland

Competing interests
The authors declare that no competing interests exist.
David Gfeller

Ludwig Centre for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland

For correspondence
david.gfeller@unil.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3952-0930

Funding

Center for Advanced Modelling Science

Julien Racle
David Gfeller

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Project grant 31003A_173156)

Julien Racle
David Gfeller

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Patients involved in this study agreed to donate metastatic tissues upon informed consent, based on dedicated clinical investigation protocols established according to the relevant regulatory standards. The protocols were approved by the local IRB, i.e. the Commission cantonale d'éthique de la recherche sur l'être humain du Canton de Vaud.

Reviewing Editor

Alfonso Valencia, Barcelona Supercomputing Center - BSC, Spain

Publication history

Received: March 2, 2017
Accepted: November 10, 2017
Accepted Manuscript published: November 13, 2017 (version 1)
Version of Record published: December 6, 2017 (version 2)

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.