Format

Send to

Choose Destination
JCI Insight. 2016 Mar 17;1(3):e85902.

Claudin-low bladder tumors are immune infiltrated and actively immune suppressed.

Author information

1
Lineberger Comprehensive Cancer Center,; Department of Genetics.
2
Lineberger Comprehensive Cancer Center,; Department of Microbiology/Immunology,; Curriculum in Bioinformatics and Computational Biology.
3
Lineberger Comprehensive Cancer Center.
4
Lineberger Comprehensive Cancer Center,; Department of Medicine, Division of Hematology/Oncology, and; Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
5
Lineberger Comprehensive Cancer Center,; Department of Genetics,; Department of Medicine, Division of Hematology/Oncology, and; Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
6
Lineberger Comprehensive Cancer Center,; Department of Medicine, Division of Hematology/Oncology, and.

Abstract

We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression. This did not appear to be due to differences in predicted neoantigen burden, but rather was associated with broad upregulation of cytokine and chemokine levels from low PPARG activity, allowing unopposed NFKB activity. Taken together, these results define a molecular subtype of bladder cancer with distinct molecular features and an immunologic profile that would, in theory, be primed for immunotherapeutic response.

PMID:
27699256
PMCID:
PMC5033914
DOI:
10.1172/jci.insight.85902
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center