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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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
23 September 2019
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| In: |
Cancer immunology immunotherapy
Year: 2019, Jahrgang: 68, Heft: 10, Pages: 1621-1633 |
| ISSN: | 1432-0851 |
| DOI: | 10.1007/s00262-019-02393-x |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1007/s00262-019-02393-x
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| Verfasserangaben: | 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 |
MARC
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| 245 | 1 | 4 | |a The BRCA2 mutation status shapes the immune phenotype of prostate cancer |c 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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| 520 | |a 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. | ||
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