| Literature DB >> 29628290 |
Vésteinn Thorsson1, David L Gibbs2, Scott D Brown3, Denise Wolf4, Dante S Bortone5, Tai-Hsien Ou Yang6, Eduard Porta-Pardo7, Galen F Gao8, Christopher L Plaisier9, James A Eddy10, Elad Ziv11, Aedin C Culhane12, Evan O Paull13, I K Ashok Sivakumar14, Andrew J Gentles15, Raunaq Malhotra16, Farshad Farshidfar17, Antonio Colaprico18, Joel S Parker5, Lisle E Mose5, Nam Sy Vo19, Jianfang Liu20, Yuexin Liu19, Janet Rader21, Varsha Dhankani2, Sheila M Reynolds2, Reanne Bowlby3, Andrea Califano13, Andrew D Cherniack8, Dimitris Anastassiou6, Davide Bedognetti22, Younes Mokrab22, Aaron M Newman23, Arvind Rao19, Ken Chen19, Alexander Krasnitz24, Hai Hu20, Tathiane M Malta25, Houtan Noushmehr25, Chandra Sekhar Pedamallu26, Susan Bullman26, Akinyemi I Ojesina27, Andrew Lamb10, Wanding Zhou28, Hui Shen28, Toni K Choueiri26, John N Weinstein19, Justin Guinney10, Joel Saltz29, Robert A Holt3, Charles S Rabkin30, Alexander J Lazar31, Jonathan S Serody32, Elizabeth G Demicco33, Mary L Disis34, Benjamin G Vincent35, Ilya Shmulevich36.
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.Entities:
Keywords: cancer genomics; immune subtypes; immuno-oncology; immunomodulatory; immunotherapy; integrative network analysis; tumor immunology; tumor microenvironment
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Year: 2018 PMID: 29628290 PMCID: PMC5982584 DOI: 10.1016/j.immuni.2018.03.023
Source DB: PubMed Journal: Immunity ISSN: 1074-7613 Impact factor: 43.474