The Immune Landscape of Cancer


Vésteinn Thorsson, Institute for Systems Biology
David L. Gibbs, Institute for Systems Biology
Scott D. Brown, British Columbia Cancer Agency
Denise Wolf, University of California, San Francisco
Dante S. Bortone, The University of North Carolina at Chapel Hill
Tai Hsien Ou Yang, Columbia University in the City of New York
Eduard Porta-Pardo, Centro Nacional de Supercomputación
Galen F. Gao, Massachusetts Institute of Technology
Christopher L. Plaisier, Institute for Systems Biology
James A. Eddy, Sage Bionetworks
Elad Ziv, UCSF Helen Diller Family Comprehensive Cancer Center
Aedin C. Culhane, Dana-Farber Cancer Institute
Evan O. Paull, Irving Cancer Research Center
I. K.Ashok Sivakumar, Johns Hopkins University
Andrew J. Gentles, Stanford University
Raunaq Malhotra, Seven Bridges Genomics Inc.
Farshad Farshidfar, University of Calgary
Antonio Colaprico, Université libre de Bruxelles (ULB)
Joel S. Parker, The University of North Carolina at Chapel Hill
Lisle E. Mose, The University of North Carolina at Chapel Hill
Nam Sy Vo, University of Texas MD Anderson Cancer Center
Jianfang Liu, Chan Soon-Shiong Institute of Molecular Medicine at Windber
Yuexin Liu, University of Texas MD Anderson Cancer Center
Janet Rader, Medical College of Wisconsin
Varsha Dhankani, Institute for Systems Biology
Sheila M. Reynolds, Institute for Systems Biology
Reanne Bowlby, British Columbia Cancer Agency
Andrea Califano, Irving Cancer Research Center
Andrew D. Cherniack, Massachusetts Institute of Technology
Dimitris Anastassiou, Columbia University in the City of New York
Davide Bedognetti, Sidra Medical and Research Center
Arvind Rao, University of Texas MD Anderson Cancer Center
Ken Chen, University of Texas MD Anderson Cancer Center

Document Type

Journal Article

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cancer genomics; immune subtypes; immuno-oncology; immunomodulatory; immunotherapy; integrative network analysis; tumor immunology; tumor microenvironment


© 2018 The Authors We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field. Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy.

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