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

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 , , and mutations; increased frequency...

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Bibliographic Details
Published in:JCI insight 2016-03, Vol.1 (3), p.e85902-e85902
Main Authors: Kardos, Jordan, Chai, Shengjie, Mose, Lisle E, Selitsky, Sara R, Krishnan, Bhavani, Saito, Ryoichi, Iglesia, Michael D, Milowsky, Matthew I, Parker, Joel S, Kim, William Y, Vincent, Benjamin G
Format: Article
Language:English
Subjects:
Antigens, Neoplasm - metabolism
Chemokines - immunology
Claudins - genetics
Cytokines - immunology
Humans
Immune Tolerance
Leukocytes - immunology
NF-kappa B - metabolism
PPAR gamma - metabolism
Tumor Microenvironment
Urinary Bladder Neoplasms - classification
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - immunology
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Summary: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 , , and mutations; increased frequency of amplification; decreased rates of , , and mutations; and decreased frequency of 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 activity, allowing unopposed 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.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.85902