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The BRCA2 mutation status shapes the immune phenotype of prostate cancer

Defects in DNA damage repair caused by mutations in BRCA1/2, ATM or other genes have been shown to play an important role in the development and progression of prostate cancer. The influence of such mutations on anti-tumor immunity in prostate cancer, however, is largely unknown. To better understan...

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Main Authors: Jenzer, Maximilian (Author) , Keß, Peter (Author) , Nientiedt, Cathleen (Author) , Endris, Volker (Author) , Kippenberger, Maximilian (Author) , Leichsenring, Jonas (Author) , Stögbauer, Fabian (Author) , Haimes, Josh (Author) , Mishkin, Skyler (Author) , Kudlow, Brian (Author) , Kaczorowski, Adam (Author) , Zschäbitz, Stefanie (Author) , Volckmar, Anna-Lena (Author) , Sültmann, Holger (Author) , Jäger, Dirk (Author) , Duensing, Anette (Author) , Schirmacher, Peter (Author) , Hohenfellner, Markus (Author) , Grüllich, Carsten (Author) , Stenzinger, Albrecht (Author) , Duensing, Stefan (Author)
Format: Article (Journal)
Language:English
Published: 23 September 2019
In: Cancer immunology immunotherapy
Year: 2019, Volume: 68, Issue: 10, Pages: 1621-1633
ISSN:1432-0851
DOI:10.1007/s00262-019-02393-x
Online Access:Verlag, Volltext: https://doi.org/10.1007/s00262-019-02393-x
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Author Notes:Maximilian Jenzer, Peter Keß, Cathleen Nientiedt, Volker Endris, Maximilian Kippenberger, Jonas Leichsenring, Fabian Stögbauer, Josh Haimes, Skyler Mishkin, Brian Kudlow, Adam Kaczorowski, Stefanie Zschäbitz, Anna-Lena Volckmar, Holger Sültmann, Dirk Jäger, Anette Duensing, Peter Schirmacher, Markus Hohenfellner, Carsten Grüllich, Albrecht Stenzinger, Stefan Duensing
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Summary:Defects in DNA damage repair caused by mutations in BRCA1/2, ATM or other genes have been shown to play an important role in the development and progression of prostate cancer. The influence of such mutations on anti-tumor immunity in prostate cancer, however, is largely unknown. To better understand the correlation between BRCA1/2 mutations and the immune phenotype in prostate cancer, we characterized the immune infiltrate of eight BRCA2-mutated tumors in comparison with eight BRCA1/2 wild-type patients by T-cell receptor sequencing and immunohistochemistry for CD45, CD4, CD8, FOXP3, and CD163. In addition, we analyzed seven prostate cancer biopsies that were either BRCA2 or ATM-mutated in comparison with wild-type tumors. Whereas in BRCA1/2 wild-type tumors, immune cells were found predominantly extratumorally, most BRCA2-mutated tumors including one biopsy showed a significantly increased intratumoral immune cell infiltration. The ratio of intratumoral to extratumoral immune cells was considerably higher in BRCA2-mutated tumors for all markers and reached statistical significance for CD4 (p = 0.007), CD8 (p = 0.006), and FOXP3 (p = 0.001). However, the intratumoral CD8 to FOXP3 ratio showed a trend to be lower in BRCA2-mutated tumors suggesting a more suppressed tumor immune microenvironment. Our findings provide a rationale for the future use of immune oncological approaches in BRCA2-mutated prostate cancer and may encourage efforts to target immunosuppressive T-cell populations to prime tumors for immunotherapy.
Item Description:Gesehen am 04.02.2020
Physical Description:Online Resource
ISSN:1432-0851
DOI:10.1007/s00262-019-02393-x

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