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The immune landscape of cancer

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Title: The immune landscape of cancer
Authors: Thorsson, V
Gibbs, DL
Brown, SD
Wolf, D
Bortone, DS
Yang, T-HO
Porta-Pardo, E
Gao, GF
Plaisier, CL
Eddy, JA
Ziv, E
Culhane, AC
Paull, EO
Sivakumar, IKA
Gentles, AJ
Malhotra, R
Farshidfar, F
Colaprico, A
Parker, JS
Mose, LE
Nam, SV
Liu, J
Liu, Y
Rader, J
Dhankani, V
Reynolds, SM
Bowlby, R
Califano, A
Cherniack, AD
Anastassiou, D
Bedognetti, D
Rao, A
Chen, K
Krasnitz, A
Hu, H
Malta, TM
Noushmehr, H
Pedamallu, CS
Bullman, S
Ojesina, AI
Lamb, A
Zhou, W
Shen, H
Choueiri, TK
Weinstein, JN
Guinney, J
Saltz, J
Holt, RA
Rabkin, CE
Lazar, AJ
Serody, JS
Demicco, EG
Disis, ML
Vincent, BG
Shmulevich, L
Item Type: Journal Article
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.
Issue Date: 17-Apr-2018
Date of Acceptance: 21-Mar-2018
URI: http://hdl.handle.net/10044/1/71213
DOI: https://doi.org/10.1016/j.immuni.2018.03.023
ISSN: 1074-7613
Publisher: Elsevier
Start Page: 812
End Page: 830.e14
Journal / Book Title: Immunity
Volume: 48
Issue: 4
Copyright Statement: © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
T-CELL-RECEPTOR
COMPREHENSIVE ANALYSIS
REGULATORY NETWORK
SOMATIC MUTATIONS
GENOMIC ANALYSES
SEQUENCING DATA
PREDICTION
REVEALS
CLASSIFICATION
INFORMATION
cancer genomics
immune subtypes
immuno-oncology
immunomodulatory
immunotherapy
integrative network analysis
tumor immunology
tumor microenvironment
Adolescent
Adult
Aged
Aged, 80 and over
Child
Female
Genomics
Humans
Interferon-gamma
Macrophages
Male
Middle Aged
Neoplasms
Prognosis
Th1-Th2 Balance
Transforming Growth Factor beta
Wound Healing
Young Adult
Cancer Genome Atlas Research Network
Macrophages
Humans
Neoplasms
Transforming Growth Factor beta
Prognosis
Genomics
Wound Healing
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
Child
Female
Male
Interferon-gamma
Young Adult
Th1-Th2 Balance
Science & Technology
Life Sciences & Biomedicine
Immunology
T-CELL-RECEPTOR
COMPREHENSIVE ANALYSIS
REGULATORY NETWORK
SOMATIC MUTATIONS
GENOMIC ANALYSES
SEQUENCING DATA
PREDICTION
REVEALS
CLASSIFICATION
INFORMATION
1107 Immunology
Immunology
Publication Status: Published
Open Access location: https://www.cell.com/immunity/fulltext/S1074-7613(18)30121-3?_returnURL=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1074761318301213%3Fshowall%3Dtrue
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer