The Immune Landscape of Cancer

Vesteinn Thorsson; David L Gibbs; Scott D Brown; Denise Wolf; Dante S Bortone; Tai-Hsien Ou Yang; Eduard Porta-Pardo; Galen F Gao; Christopher L Plaisier; James A Eddy; Elad Ziv; Aedin C Culhane; Evan O Paull; IK Ashok Sivakumar; Andrew J Gentles; Raunaq Malhotra; Farshad Farshidfar; Antonio Colaprico; Joel S Parker; Lisle E Mose; Sy Vo Nam; Jianfang Liu; Yuexin Liu; Janet Rader; Varsha Dhankani; Sheila M Reynolds; Reanne Bowlby; Andrea Califano; Andrew D Cherniack; Dimitris Anastassiou; Davide Bedognetti; Arvind Rao; Ken Chen; Alexander Krasnitz; Hai Hu; Tathiane M Malta; Houtan Noushmehr; Chandra Sekhar Pedamallu; Susan Bullman; Akinyemi I Ojesina; Andrew Lamb; Wanding Zhou; Hui Shen; Toni K Choueiri; John N Weinstein; Justin Guinney; Joel Saltz; Robert A Holt; Charles E Rabkin; Alexander J Lazar; Jonathan S Serody; Elizabeth G Demicco; Mary L Disis; Benjamin G Vincent; Llya Shmulevich

Journal article

The Immune Landscape of Cancer

Vesteinn Thorsson, David L Gibbs, Scott D Brown, Denise Wolf, Dante S Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F Gao, Christopher L Plaisier, James A Eddy, Elad Ziv, Aedin C Culhane, Evan O Paull, IK Ashok Sivakumar, Andrew J Gentles, Raunaq Malhotra, Farshad Farshidfar, Antonio Colaprico, Joel S Parker, Lisle E Mose Show all

IMMUNITY | CELL PRESS | Published : 2018

DOI: 10.1016/j.immuni.2018.03.023

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. M..

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University of Melbourne Researchers

Christopher Hovens Author

Michael Lawrence Author

Grants

Awarded by Institute for Systems Biology-Cancer Genomics Cloud (ISB-CGC)

Awarded by NCI

Awarded by US Department of Defense through the Henry M. Jackson Foundation for the Advancement of Military Medicine

Awarded by Seven Bridges Cancer Genomics Cloud

Awarded by NATIONAL CANCER INSTITUTE

Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE

Awarded by NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

Awarded by NATIONAL LIBRARY OF MEDICINE

Awarded by OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH

Funding Acknowledgements

We are grateful to all the patients and families who contributed to this study. We also thank the Office of Cancer Genomics at the NCI for organizational and logistical support of this study. The high-throughput analyses in this study were performed on the Institute for Systems Biology-Cancer Genomics Cloud (ISB-CGC) under contract number HHSN261201400007C and on the Seven Bridges Cancer Genomics Cloud under contract HHSN261201400008C, with federal funds from the National Cancer Institute, NIH, Department of Health and Human Services. Funding from the Cancer Research Institute is gratefully acknowledged, as is support from NCI through U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672. The study was supported by W81XWH-12-2-0050, HU0001-16-2-0004 from the US Department of Defense through the Henry M. Jackson Foundation for the Advancement of Military Medicine. We thank Peter Hammerman and Yasin Sxenbabaoglu for contributions in early phases of this work.