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

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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.

In: DIS MARKERS, Vol. 2019, 2019, p. 2532518.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mandelkow, T, Blessin, NC, Lueerss, E, Pott, L, Simon, R, Li, W, Wellge, B, Debatin, NF, Höflmayer, D, Izbicki, JR, Büscheck, F, Luebke, AM, Wittmer, C, Jacobsen, F, Lutz, F, Burandt, E, Steurer, S, Sauter, G, Tsourlakis, MC, Wilczak, W, Hinsch, A & Minner, S 2019, 'Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder', DIS MARKERS, vol. 2019, pp. 2532518. https://doi.org/10.1155/2019/2532518

APA

Mandelkow, T., Blessin, N. C., Lueerss, E., Pott, L., Simon, R., Li, W., Wellge, B., Debatin, N. F., Höflmayer, D., Izbicki, J. R., Büscheck, F., Luebke, A. M., Wittmer, C., Jacobsen, F., Lutz, F., Burandt, E., Steurer, S., Sauter, G., Tsourlakis, M. C., ... Minner, S. (2019). Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder. DIS MARKERS, 2019, 2532518. https://doi.org/10.1155/2019/2532518

Vancouver

Mandelkow T, Blessin NC, Lueerss E, Pott L, Simon R, Li W et al. Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder. DIS MARKERS. 2019;2019:2532518. https://doi.org/10.1155/2019/2532518

Bibtex

@article{85234bfbcb4441c99ccd9b30c9195723,
title = "Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder",
abstract = "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/mm2) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625 ± 800, p < 0.001; CD8: 362 ± 626 cells/mm2, 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/mm2; urothelial carcinomas CD3: 1167 ± 1206, p = 0.31; CD8: 582 ± 864 cells/mm2, 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/mm2 to 50-109 CD3-positive cells/mm2 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.",
author = "Tim Mandelkow and Blessin, {Niclas C} and Eva Lueerss and Laura Pott and Ronald Simon and Wenchao Li and Bj{\"o}rn Wellge and Debatin, {Nicolaus F} and Doris H{\"o}flmayer and Izbicki, {Jakob R} and Franziska B{\"u}scheck and Luebke, {Andreas M} and Corinna Wittmer and Frank Jacobsen and Florian Lutz and Eike Burandt and Stefan Steurer and Guido Sauter and Tsourlakis, {Maria Christina} and Waldemar Wilczak and Andrea Hinsch and Sarah Minner",
year = "2019",
doi = "10.1155/2019/2532518",
language = "English",
volume = "2019",
pages = "2532518",
journal = "DIS MARKERS",
issn = "0278-0240",
publisher = "IOS Press",

}

RIS

TY - JOUR

T1 - Immune Exclusion Is Frequent in Small-Cell Carcinoma of the Bladder

AU - Mandelkow, Tim

AU - Blessin, Niclas C

AU - Lueerss, Eva

AU - Pott, Laura

AU - Simon, Ronald

AU - Li, Wenchao

AU - Wellge, Björn

AU - Debatin, Nicolaus F

AU - Höflmayer, Doris

AU - Izbicki, Jakob R

AU - Büscheck, Franziska

AU - Luebke, Andreas M

AU - Wittmer, Corinna

AU - Jacobsen, Frank

AU - Lutz, Florian

AU - Burandt, Eike

AU - Steurer, Stefan

AU - Sauter, Guido

AU - Tsourlakis, Maria Christina

AU - Wilczak, Waldemar

AU - Hinsch, Andrea

AU - Minner, Sarah

PY - 2019

Y1 - 2019

N2 - 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/mm2) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625 ± 800, p < 0.001; CD8: 362 ± 626 cells/mm2, 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/mm2; urothelial carcinomas CD3: 1167 ± 1206, p = 0.31; CD8: 582 ± 864 cells/mm2, 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/mm2 to 50-109 CD3-positive cells/mm2 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.

AB - 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/mm2) was more than 3 times lower than that in the urothelial carcinomas (CD3: 625 ± 800, p < 0.001; CD8: 362 ± 626 cells/mm2, 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/mm2; urothelial carcinomas CD3: 1167 ± 1206, p = 0.31; CD8: 582 ± 864 cells/mm2, 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/mm2 to 50-109 CD3-positive cells/mm2 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.

U2 - 10.1155/2019/2532518

DO - 10.1155/2019/2532518

M3 - SCORING: Journal article

C2 - 31191745

VL - 2019

SP - 2532518

JO - DIS MARKERS

JF - DIS MARKERS

SN - 0278-0240

ER -