Early Detection Research Network

The Immune Landscape of Cancer.

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.

Anastassiou D, Bedognetti D, Bortone DS, Bowlby R, Brown SD, Bullman S, Califano A, Chen K, Cherniack AD, Choueiri TK, Colaprico A, Culhane AC, Demicco EG, Dhankani V, Disis ML, Eddy JA, Farshidfar F, Gao GF, Gentles AJ, Gibbs DL, Guinney J, Holt RA, Hu H, Krasnitz A, Lamb A, Lazar AJ, Liu J, Liu Y, Malhotra R, Malta TM, Mokrab Y, Mose LE, Newman AM, Noushmehr H, Ojesina AI, Ou Yang TH, Parker JS, Paull EO, Pedamallu CS, Plaisier CL, Porta-Pardo E, Rabkin CS, Rader J, Rao A, Reynolds SM, Saltz J, Serody JS, Shen H, Shmulevich I, Sivakumar IKA, Thorsson V, Vincent BG, Vo NS, Weinstein JN, Wolf D, Zhou W, Ziv E

29628290

Immunity, 2018, 48 (4)

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