The Immune Landscape of Cancer.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Thorsson, V; Gibbs, DL; Brown, SD; Wolf, D; Bortone, DS; Ou Yang, T-H; 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; Vo, NS; 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; Cancer Genome Atlas Research Network, ; Lazar, AJ; Serody, JS; Demicco, EG; Disis, ML; Vincent, BG; Shmulevich, L

Published Date

  • April 5, 2018

Published In

Volume / Issue

  • 48 / 4

Start / End Page

  • 812 - 830.e14

PubMed ID

  • 29628290

Pubmed Central ID

  • 29628290

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2018.03.023

Language

  • eng