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Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder

Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It is currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors of response...

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Autores principales: Mandelkow, Tim, Blessin, Niclas C., Lueerss, Eva, Pott, Laura, Simon, Ronald, Li, Wenchao, Wellge, Björn, Debatin, Nicolaus F., Höflmayer, Doris, Izbicki, Jakob R., Büscheck, Franziska, Luebke, Andreas M., Wittmer, Corinna, Jacobsen, Frank, Lutz, Florian, Burandt, Eike, Steurer, Stefan, Sauter, Guido, Tsourlakis, Maria Christina, Wilczak, Waldemar, Hinsch, Andrea, Minner, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525886/
https://www.ncbi.nlm.nih.gov/pubmed/31191745
http://dx.doi.org/10.1155/2019/2532518
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author Mandelkow, Tim
Blessin, Niclas C.
Lueerss, Eva
Pott, Laura
Simon, Ronald
Li, Wenchao
Wellge, Björn
Debatin, Nicolaus F.
Höflmayer, Doris
Izbicki, Jakob R.
Büscheck, Franziska
Luebke, Andreas M.
Wittmer, Corinna
Jacobsen, Frank
Lutz, Florian
Burandt, Eike
Steurer, Stefan
Sauter, Guido
Tsourlakis, Maria Christina
Wilczak, Waldemar
Hinsch, Andrea
Minner, Sarah
author_facet Mandelkow, Tim
Blessin, Niclas C.
Lueerss, Eva
Pott, Laura
Simon, Ronald
Li, Wenchao
Wellge, Björn
Debatin, Nicolaus F.
Höflmayer, Doris
Izbicki, Jakob R.
Büscheck, Franziska
Luebke, Andreas M.
Wittmer, Corinna
Jacobsen, Frank
Lutz, Florian
Burandt, Eike
Steurer, Stefan
Sauter, Guido
Tsourlakis, Maria Christina
Wilczak, Waldemar
Hinsch, Andrea
Minner, Sarah
author_sort Mandelkow, Tim
collection PubMed
description Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It is currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors of response including PD-L1 expression and the quantity and location of tumor-infiltrating lymphocytes (TILs) in 12 small-cell and 69 “classical” urothelial cancers by immunohistochemistry. The analysis revealed that small-cell carcinomas were characterized by the virtual absence of PD-L1 expression and an “immune-excluded” phenotype with only a few TILs in the center of the tumor (CT). In small-cell carcinomas, the average immune cell density in the CT (CD3: 159 ± 206, CD8: 87 ± 169 cells/mm(2)) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625 ± 800, p < 0.001; CD8: 362 ± 626 cells/mm(2), p = 0.004) while there was no significant difference in the immune cell density at the invasive margin (IM) (small-cell carcinomas CD3: 899 ± 733, CD8: 404 ± 433 cells/mm(2); urothelial carcinomas CD3: 1167 ± 1206, p = 0.31; CD8: 582 ± 864 cells/mm(2), p = 0.27). Positive PD-L1 staining was found in 39% of urothelial cancers, but in only 8% of small-cell bladder cancer cases (p = 0.04). Concordant with these data, a sharp decrease of PD-L1 positivity from >80% to 0% positive cells and of TILS in the CT from 466-1063 CD3-positive cells/mm(2) to 50-109 CD3-positive cells/mm(2) was observed in two cancers with clear-cut progression from “classical” urothelial to small-cell carcinoma. In conclusion, these data demonstrate that small-cell bladder cancer commonly exhibits an immune-excluded phenotype.
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spelling pubmed-65258862019-06-12 Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder Mandelkow, Tim Blessin, Niclas C. Lueerss, Eva Pott, Laura Simon, Ronald Li, Wenchao Wellge, Björn Debatin, Nicolaus F. Höflmayer, Doris Izbicki, Jakob R. Büscheck, Franziska Luebke, Andreas M. Wittmer, Corinna Jacobsen, Frank Lutz, Florian Burandt, Eike Steurer, Stefan Sauter, Guido Tsourlakis, Maria Christina Wilczak, Waldemar Hinsch, Andrea Minner, Sarah Dis Markers Research Article Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It is currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors of response including PD-L1 expression and the quantity and location of tumor-infiltrating lymphocytes (TILs) in 12 small-cell and 69 “classical” urothelial cancers by immunohistochemistry. The analysis revealed that small-cell carcinomas were characterized by the virtual absence of PD-L1 expression and an “immune-excluded” phenotype with only a few TILs in the center of the tumor (CT). In small-cell carcinomas, the average immune cell density in the CT (CD3: 159 ± 206, CD8: 87 ± 169 cells/mm(2)) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625 ± 800, p < 0.001; CD8: 362 ± 626 cells/mm(2), p = 0.004) while there was no significant difference in the immune cell density at the invasive margin (IM) (small-cell carcinomas CD3: 899 ± 733, CD8: 404 ± 433 cells/mm(2); urothelial carcinomas CD3: 1167 ± 1206, p = 0.31; CD8: 582 ± 864 cells/mm(2), p = 0.27). Positive PD-L1 staining was found in 39% of urothelial cancers, but in only 8% of small-cell bladder cancer cases (p = 0.04). Concordant with these data, a sharp decrease of PD-L1 positivity from >80% to 0% positive cells and of TILS in the CT from 466-1063 CD3-positive cells/mm(2) to 50-109 CD3-positive cells/mm(2) was observed in two cancers with clear-cut progression from “classical” urothelial to small-cell carcinoma. In conclusion, these data demonstrate that small-cell bladder cancer commonly exhibits an immune-excluded phenotype. Hindawi 2019-05-02 /pmc/articles/PMC6525886/ /pubmed/31191745 http://dx.doi.org/10.1155/2019/2532518 Text en Copyright © 2019 Tim Mandelkow et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mandelkow, Tim
Blessin, Niclas C.
Lueerss, Eva
Pott, Laura
Simon, Ronald
Li, Wenchao
Wellge, Björn
Debatin, Nicolaus F.
Höflmayer, Doris
Izbicki, Jakob R.
Büscheck, Franziska
Luebke, Andreas M.
Wittmer, Corinna
Jacobsen, Frank
Lutz, Florian
Burandt, Eike
Steurer, Stefan
Sauter, Guido
Tsourlakis, Maria Christina
Wilczak, Waldemar
Hinsch, Andrea
Minner, Sarah
Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder
title Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder
title_full Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder
title_fullStr Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder
title_full_unstemmed Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder
title_short Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder
title_sort immune exclusion is frequent in small-cell carcinoma of the bladder
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525886/
https://www.ncbi.nlm.nih.gov/pubmed/31191745
http://dx.doi.org/10.1155/2019/2532518
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