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