The BRCA2 mutation status shapes the immune phenotype of prostate cancer

• Verfasst von: Jenzer, Maximilian [VerfasserIn]
• Verfasst von: Keß, Peter [VerfasserIn]
• Verfasst von: Nientiedt, Cathleen [VerfasserIn]
• Verfasst von: Endris, Volker [VerfasserIn]
• Verfasst von: Kippenberger, Maximilian [VerfasserIn]
• Verfasst von: Leichsenring, Jonas [VerfasserIn]
• Verfasst von: Stögbauer, Fabian [VerfasserIn]
• Verfasst von: Haimes, Josh [VerfasserIn]
• Verfasst von: Mishkin, Skyler [VerfasserIn]
• Verfasst von: Kudlow, Brian [VerfasserIn]
• Verfasst von: Kaczorowski, Adam [VerfasserIn]
• Verfasst von: Zschäbitz, Stefanie [VerfasserIn]
• Verfasst von: Volckmar, Anna-Lena [VerfasserIn]
• Verfasst von: Sültmann, Holger [VerfasserIn]
• Verfasst von: Jäger, Dirk [VerfasserIn]
• Verfasst von: Duensing, Anette [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Hohenfellner, Markus [VerfasserIn]
• Verfasst von: Grüllich, Carsten [VerfasserIn]
• Verfasst von: Stenzinger, Albrecht [VerfasserIn]
• Verfasst von: Duensing, Stefan [VerfasserIn]
• Titel: The BRCA2 mutation status shapes the immune phenotype of prostate cancer
• Verf.angabe: 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
• E-Jahr: 2019
• Jahr: 23 September 2019
• Umfang: 13 S.
• Fussnoten: Gesehen am 04.02.2020
• Titel Quelle: Enthalten in: Cancer immunology immunotherapy
• Ort Quelle: Berlin : Springer, 1976
• Jahr Quelle: 2019
• Band/Heft Quelle: 68(2019), 10, Seite 1621-1633
• ISSN Quelle: 1432-0851
• DOI: doi:10.1007/s00262-019-02393-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1689231246

Abstract

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.