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Updated: Nov 1, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Mismatch repair-deficient prostate cancer with parenchymal brain metastases treated with immune checkpoint blockade
Laura A Sena1,2, Daniela C Salles1, Elizabeth L Engle2,3
1The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Abstract:
Parenchymal brain metastases from prostate cancer are unusual and are associated with poor prognosis. Given the rarity of this entity, little is known about its molecular and histologic characteristics. Here we describe a patient with metastatic castration-resistant, mismatch repair-deficient (dMMR) prostate cancer with parenchymal brain metastases. Analysis of a brain metastasis revealed MLH1 loss consistent with dMMR, yet few tumor-infiltrating lymphocytes (TILs). He was treated with immune checkpoint blockade (ICB) and exhibited an extra-central nervous system (CNS) systemic response but CNS progression. Subsequent assessment of a brain metastasis following ICB treatment surprisingly showed increased TIL density and depletion of macrophages, suggestive of an enhanced antitumor immune response. Post-treatment tumoral DNA sequencing did not reveal acquired mutations that might confer resistance to ICB. This is the first description of ICB therapy for a patient with prostate cancer with parenchymal brain metastases, with pre- and post-treatment immunogenomic analyses.
Insights
This study details a rare case of brain metastases in prostate cancer. Immune checkpoint blockade showed a systemic response but not in the brain, despite post-treatment immune changes.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Parenchymal brain metastases from prostate cancer are rare and linked to poor outcomes.
- Limited data exists on the molecular and histological features of these metastases.
Observation:
- A patient with metastatic castration-resistant, mismatch repair-deficient (dMMR) prostate cancer presented with parenchymal brain metastases.
- Initial analysis showed MLH1 loss (dMMR) with few tumor-infiltrating lymphocytes (TILs).
Findings:
- Immune checkpoint blockade (ICB) yielded an extra-CNS response but CNS progression.
- Post-ICB brain metastasis revealed increased TILs and macrophage depletion, indicating an enhanced immune response.
- No acquired resistance mutations were found post-treatment.
Implications:
- This is the first report of ICB for prostate cancer with brain metastases, including pre- and post-treatment immunogenomic analysis.
- Findings suggest potential immune responses within the CNS to ICB, warranting further investigation.
