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Updated: Jan 19, 2026

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
08:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

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The BRCA2 mutation status shapes the immune phenotype of prostate cancer

Maximilian Jenzer1,2, Peter Keß1, Cathleen Nientiedt1,2

  • 1Section of Molecular Urooncology, Department of Urology, University of Heidelberg School of Medicine, Im Neuenheimer Feld 517, 69120, Heidelberg, Germany.

Cancer Immunology, Immunotherapy : CII
|September 25, 2019
PubMed

Insights

Prostate cancer with BRCA2 mutations shows increased immune cell infiltration within tumors, unlike wild-type cancers. This suggests potential for immune therapies targeting BRCA2-mutated prostate tumors.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • DNA damage repair gene mutations (BRCA1/2, ATM) are implicated in prostate cancer development.
  • The impact of these mutations on anti-tumor immunity in prostate cancer remains largely unexplored.

Purpose of the Study:

  • To investigate the relationship between BRCA1/2 mutations and the immune microenvironment in prostate cancer.
  • To compare immune cell infiltration patterns in BRCA2-mutated versus wild-type prostate tumors.

Main Methods:

  • Characterization of immune infiltrates using T-cell receptor sequencing and immunohistochemistry (CD45, CD4, CD8, FOXP3, CD163).
  • Analysis of eight BRCA2-mutated tumors against eight BRCA1/2 wild-type tumors.
  • Comparison of seven BRCA2 or ATM-mutated prostate cancer biopsies with wild-type tumors.

Main Results:

  • BRCA2-mutated tumors exhibited significantly higher intratumoral immune cell infiltration compared to extratumoral infiltration seen in wild-type tumors.
  • The ratio of intratumoral to extratumoral immune cells was significantly higher for CD4, CD8, and FOXP3 markers in BRCA2-mutated tumors.
  • A trend towards a lower intratumoral CD8 to FOXP3 ratio in BRCA2-mutated tumors suggests a more suppressed immune microenvironment.

Conclusions:

  • BRCA2 mutations alter the immune cell distribution within prostate tumors, increasing intratumoral infiltration.
  • Findings support the potential application of immunooncology approaches for BRCA2-mutated prostate cancer.
  • Targeting immunosuppressive T-cell populations may enhance treatment efficacy in these patients.
Keywords:
BRCA1/2Homologous recombination deficiencyImmune checkpoint inhibitorsProstate cancerTumor microenvironmentTumor-infiltrating lymphocytes

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