title: Claudin-low bladder tumors are immune infiltrated and actively immune suppressed.
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 ofRB1,EP300, andNCOR1mutations; increased frequency ofEGFRamplification; decreased rates ofFGFR3,ELF3, andKDM6Amutations; and decreased frequency ofPPARGamplification. 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 lowPPARGactivity, allowing unopposedNFKBactivity. 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.
authors.affiliation: Lineberger Comprehensive Cancer Center.|Department of Genetics.
authors.forename: Jordan
authors.initials: J
authors.lastname: Kardos
authors.affiliation: Lineberger Comprehensive Cancer Center.|Department of Microbiology/Immunology.|Curriculum in Bioinformatics and Computational Biology.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Chai
authors.affiliation: Lineberger Comprehensive Cancer Center.
authors.forename: Lisle E
authors.initials: LE
authors.lastname: Mose
authors.affiliation: Lineberger Comprehensive Cancer Center.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Selitsky
authors.affiliation: Lineberger Comprehensive Cancer Center.
authors.forename: Bhavani
authors.initials: B
authors.lastname: Krishnan
authors.affiliation: Lineberger Comprehensive Cancer Center.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Saito
authors.affiliation: Lineberger Comprehensive Cancer Center.|Department of Genetics.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Iglesia
authors.affiliation: 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.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.affiliation: Lineberger Comprehensive Cancer Center.|Department of Genetics.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: 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.
authors.forename: William Y
authors.initials: WY
authors.lastname: Kim
authors.affiliation: Lineberger Comprehensive Cancer Center.|Department of Medicine, Division of Hematology/Oncology, and.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Vincent
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D018925:Chemokines / Q000276:immunology; D057167:Claudins / Q000235:genetics*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007962:Leukocytes / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D059016:Tumor Microenvironment; D001749:Urinary Bladder Neoplasms / Q000145:classification / Q000235:genetics* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018925:Chemokines; D057167:Claudins; D016207:Cytokines; D016328:NF-kappa B; D047495:PPAR gamma