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The Urothelial Tran...
The Urothelial Transcriptomic Response to Interferon Gamma : Implications for Bladder Cancer Prognosis and Immunotherapy
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- Baker, Simon C. (författare)
- University of York
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- Mason, Andrew S. (författare)
- University of York
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- Slip, Raphael G. (författare)
- University of York
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- Eriksson, Pontus (författare)
- Lund University,Lunds universitet,Genomiska analyser av urinblåscancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urothelial Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Sjödahl, Gottfrid (författare)
- Lund University,Lunds universitet,Urologi - blåscancer, Malmö,Forskargrupper vid Lunds universitet,Genomiska analyser av urinblåscancer,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Urology - urothelial cancer, Malmö,Lund University Research Groups,Urothelial Cancer Genomics,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Trejdosiewicz, Ludwik K. (författare)
- University of York
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- Southgate, Jennifer (författare)
- University of York
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(creator_code:org_t)
- 2022-10-27
- 2022
- Engelska.
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:21
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Interferon gamma (IFNγ) is central to the inflammatory immune response, such as that entrained by BCG immunotherapy for bladder cancer. However, immune-mediated tumour cell killing is subject to modulation by immunoinhibitory “checkpoint” receptors such as PD-L1. We investigated the effects of IFNγ on barrier-forming in vitro-differentiated normal human urothelium using mRNA-sequencing, and showed canonical upregulation of MHC class I/II and de novo expression of the T cell tropic CXCL9-11 chemokines. Normal urothelium constitutively expressed immunoinhibitory B7 family member VSIR (VISTA), while CD274 (PD-L1) expression was induced/upregulated by IFNγ. We generated a urothelial IFNγ response gene signature. When applied to the unsupervised clustering of non-muscle-invasive bladder cancers, the IFNγ-signature predicted longer recurrence-free survival. In muscle-invasive cancers, the IFNγ-signature split the basal/squamous consensus subtype, with significantly worse overall survival when weak or absent. This study offers novel insights into strategies to enhance immunotherapy via the IFNγ and VISTA/PD-L1 nexus.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- BCG
- bladder cancer
- immune checkpoint
- immunotherapy
- interferon gamma
- PD-L1
- urothelium
- VISTA
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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