The Immune Landscape of Cancer

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.

Full text access

Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, 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.  Immunity. 2018 Apr 17;48(4):812-830.e14. doi: 10.1016/j.immuni.2018.03.023. Epub 2018 Apr 5. PubMed  PMID: 29628290.

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

Further reading

Taha Z, J Janse van Rensburg H, Yang X. The Hippo Pathway: Immunity and Cancer. Cancers (Basel). 2018 Mar 28;10(4). pii: E94. doi: 10.3390/cancers10040094. Review. PubMed PMID: 29597279.

Schneider NFZ, Cerella C, Lee J-Y, Mazumder A, Kim KR, de Carvalho A, Munkert J, Pádua RM, Kreis W, Kim K-W, Christov C, Dicato M, Kim H-J, Han BW, Braga FC, Simões CMO and Diederich M (2018) Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death. Front. Pharmacol. 9:70. doi: 10.3389/fphar.2018.00070

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