The Immune Landscape of Cancer

Immunity. 2018 Apr 17;48(4):812-830.e14. doi: 10.1016/j.immuni.2018.03.023. Epub 2018 Apr 5.

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.

Keywords: cancer genomics; immune subtypes; immuno-oncology; immunomodulatory; immunotherapy; integrative network analysis; tumor immunology; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Female
  • Genomics / methods*
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Macrophages / immunology
  • Male
  • Middle Aged
  • Neoplasms* / classification
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Prognosis
  • Th1-Th2 Balance / physiology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Wound Healing / genetics
  • Wound Healing / immunology
  • Young Adult

Substances

  • IFNG protein, human
  • Transforming Growth Factor beta
  • Interferon-gamma

Grants and funding