The Immune Landscape of Cancer

V. Thorsson, D. L. Gibbs, S. D. Brown, D. Wolf, D. S. Bortone, T. H. Ou Yang, E. Porta-Pardo, G. F. Gao, C. L. Plaisier, J. A. Eddy, E. Ziv, A. C. Culhane, E. O. Paull, I. K. A. Sivakumar, A. J. Gentles, R. Malhotra, F. Farshidfar, A. Colaprico, J. S. Parker, L. E. MoseN. S. Vo, J. Liu, Y. Liu, J. Rader, V. Dhankani, S. M. Reynolds, R. Bowlby, A. Califano, A. D. Cherniack, D. Anastassiou, D. Bedognetti, A. Rao, K. Chen, A. Krasnitz, H. Hu, T. M. Malta, H. Noushmehr, C. S. Pedamallu, S. Bullman, A. I. Ojesina, A. Lamb, W. Zhou, H. Shen, T. K. Choueiri, J. N. Weinstein, J. Guinney, J. Saltz, R. A. Holt, C. E. Rabkin, Cancer Genome Atlas Research Network, A. J. Lazar, J. S. Serody, E. G. Demicco, M. L. Disis, B. G. Vincent, L. Shmulevich, M. (come contributors) Marino

Research output: Contribution to journalArticlepeer-review

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-gamma dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-beta 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.
Original languageEnglish
Pages (from-to)812-830.e14
JournalImmunity
Volume48
Issue number4
DOIs
Publication statusPublished - Apr 17 2018
Externally publishedYes

Keywords

  • cancer genomics
  • immune subtypes
  • immuno-oncology
  • immunomodulatory
  • immunotherapy
  • integrative network analysis
  • tumor immunology
  • tumor microenvironment

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