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.