Interleukin-17-positive mast cells influence outcomes from BCG for patients with CIS : Data from a comprehensive characterisation of the immune microenvironment of urothelial bladder cancer
The tumour immune microenvironment is considered to influence cancer behaviour and outcome. Using a panel of markers for innate and adaptive immune cells we set out to characterise and understand the bladder tumour microenvironment of 114 patients from a prospective multicentre cohort of newly-diagnosed bladder cancer patients, followed-up for 4.33±1.71 years. We found IL-17-positive cells were significantly increased in primary and concomitant carcinoma in situ (CIS), p<0.0001, a highly malignant lesion which is the most significant single risk factor for disease progression. Further characterisation of the tumour immunophenotype identified IL-17+ cells as predominantly mast cells rather than T-cells, in contrast to most other tumour types. Expression of the IL-17-receptor in bladder tumours, and functional effects and gene expression changes induced by IL-17 in bladder tumour cells in vitro suggest a role in tumour behaviour. Finally, we assessed the effects of IL-17 in the context of patient outcome, following intravesical BCG immunotherapy which is the standard of care; higher numbers of IL-17+ cells were associated with improved event-free survival (p = 0.0449, HR 0.2918, 95% CI 0.08762-0.9721) in patients with primary and concomitant CIS (n = 41), we propose a model of IL-17+ Mast cells mechanism of action. Thus, in the context of bladder CIS, IL-17+ mast cells predict favourable outcome following BCG immunotherapy indicative of a novel mechanism of BCG immunotherapy in UBC and could form the basis of a stratified approach to treatment.
| Errataetall: |
CommentIn: Nat Rev Urol. 2017 Nov;14(11):639. - PMID 28994827 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
PloS one - 12(2017), 9 vom: 19., Seite e0184841 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dowell, Alexander C [VerfasserIn] |
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| Anmerkungen: |
Date Completed 17.10.2017 Date Revised 13.11.2018 published: Electronic-eCollection CommentIn: Nat Rev Urol. 2017 Nov;14(11):639. - PMID 28994827 Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0184841 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM27601491X |
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| 500 | |a CommentIn: Nat Rev Urol. 2017 Nov;14(11):639. - PMID 28994827 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The tumour immune microenvironment is considered to influence cancer behaviour and outcome. Using a panel of markers for innate and adaptive immune cells we set out to characterise and understand the bladder tumour microenvironment of 114 patients from a prospective multicentre cohort of newly-diagnosed bladder cancer patients, followed-up for 4.33±1.71 years. We found IL-17-positive cells were significantly increased in primary and concomitant carcinoma in situ (CIS), p<0.0001, a highly malignant lesion which is the most significant single risk factor for disease progression. Further characterisation of the tumour immunophenotype identified IL-17+ cells as predominantly mast cells rather than T-cells, in contrast to most other tumour types. Expression of the IL-17-receptor in bladder tumours, and functional effects and gene expression changes induced by IL-17 in bladder tumour cells in vitro suggest a role in tumour behaviour. Finally, we assessed the effects of IL-17 in the context of patient outcome, following intravesical BCG immunotherapy which is the standard of care; higher numbers of IL-17+ cells were associated with improved event-free survival (p = 0.0449, HR 0.2918, 95% CI 0.08762-0.9721) in patients with primary and concomitant CIS (n = 41), we propose a model of IL-17+ Mast cells mechanism of action. Thus, in the context of bladder CIS, IL-17+ mast cells predict favourable outcome following BCG immunotherapy indicative of a novel mechanism of BCG immunotherapy in UBC and could form the basis of a stratified approach to treatment | ||
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| 700 | 1 | |a Wen, Kaisheng |e verfasserin |4 aut | |
| 700 | 1 | |a Devall, Adam J |e verfasserin |4 aut | |
| 700 | 1 | |a During, Vinnie |e verfasserin |4 aut | |
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| 700 | 1 | |a Cheng, Kar K |e verfasserin |4 aut | |
| 700 | 1 | |a Zeegers, Maurice P |e verfasserin |4 aut | |
| 700 | 1 | |a Bryan, Richard T |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Graham S |e verfasserin |4 aut | |
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