The Immune Landscape of Cancer

Abstract

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.

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Affiliated Institutions

• Discovery Institute US
• UCSF Helen Diller Family Comprehensive Cancer Center US
• Institute for Systems Biology US
• Harvard University US
• Université Libre de Bruxelles BE
• Windber Research Institute US
• Cold Spring Harbor Laboratory US
• University of Alabama at Birmingham US
• National Cancer Institute US
• The University of Texas MD Anderson Cancer Center US
• Universidade de São Paulo BR
• Sage Bionetworks US
• Canada's Michael Smith Genome Sciences Centre CA
• Universitat Politècnica de Catalunya ES
• Broad Institute US
• University of North Carolina at Chapel Hill US
• Cancer Research Center US
• Arizona State University US
• Sidra Medical and Research Center QA
• Van Andel Institute US
• Medical College of Wisconsin US
• Stanford University US
• Stony Brook Medicine US
• BC Cancer Agency CA
• Massachusetts Institute of Technology US
• Columbia University US
• Henry Ford Hospital US
• Division of Cancer Epidemiology and Genetics
• UNC Lineberger Comprehensive Cancer Center
• Dana-Farber Cancer Institute US
• Barcelona Supercomputing Center ES
• Seven Bridges Genomics (United States) US
• University of Calgary CA
• Mount Sinai Hospital CA
• Johns Hopkins University US
• University of Washington US
• University of California, San Francisco US

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