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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-? dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-? 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.

SUBMITTER: Thorsson V 

PROVIDER: S-EPMC5982584 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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The Immune Landscape of Cancer.

Thorsson Vésteinn V   Gibbs David L DL   Brown Scott D SD   Wolf Denise D   Bortone Dante S DS   Ou Yang Tai-Hsien TH   Porta-Pardo Eduard E   Gao Galen F GF   Plaisier Christopher L CL   Eddy James A JA   Ziv Elad E   Culhane Aedin C AC   Paull Evan O EO   Sivakumar I K Ashok IKA   Gentles Andrew J AJ   Malhotra Raunaq R   Farshidfar Farshad F   Colaprico Antonio A   Parker Joel S JS   Mose Lisle E LE   Vo Nam Sy NS   Liu Jianfang J   Liu Yuexin Y   Rader Janet J   Dhankani Varsha V   Reynolds Sheila M SM   Bowlby Reanne R   Califano Andrea A   Cherniack Andrew D AD   Anastassiou Dimitris D   Bedognetti Davide D   Mokrab Younes Y   Newman Aaron M AM   Rao Arvind A   Chen Ken K   Krasnitz Alexander A   Hu Hai H   Malta Tathiane M TM   Noushmehr Houtan H   Pedamallu Chandra Sekhar CS   Bullman Susan S   Ojesina Akinyemi I AI   Lamb Andrew A   Zhou Wanding W   Shen Hui H   Choueiri Toni K TK   Weinstein John N JN   Guinney Justin J   Saltz Joel J   Holt Robert A RA   Rabkin Charles S CS   Lazar Alexander J AJ   Serody Jonathan S JS   Demicco Elizabeth G EG   Disis Mary L ML   Vincent Benjamin G BG   Shmulevich Ilya I  

Immunity 20180405 4


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 proliferati  ...[more]

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