The Immune Landscape of Cancer.

Immunity
Authors
Keywords
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.

Year of Publication
2018
Journal
Immunity
Volume
48
Issue
4
Pages
812-830.e14
Date Published
2018 04 17
ISSN
1097-4180
DOI
10.1016/j.immuni.2018.03.023
PubMed ID
29628290
PubMed Central ID
PMC5982584
Links
Grant list
U24 CA143866 / CA / NCI NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P50 CA058223 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
HHSN261201400007C / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
R50 CA221675 / CA / NCI NIH HHS / United States
U24 CA210990 / CA / NCI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U54 CA209997 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
R01 LM009239 / LM / NLM NIH HHS / United States
U24 CA180924 / CA / NCI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
S10 OD012351 / OD / NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
HHSN261201400008C / CA / NCI NIH HHS / United States
U24 CA210957 / CA / NCI NIH HHS / United States
P30 CA045508 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
S10 OD021764 / OD / NIH HHS / United States
R01 CA163722 / CA / NCI NIH HHS / United States
R01 GM045436 / GM / NIGMS NIH HHS / United States
R35 CA197745 / CA / NCI NIH HHS / United States
K24 CA169004 / CA / NCI NIH HHS / United States