Mismatch repair-deficient prostate cancer with parenchymal brain metastases treated with immune checkpoint blockade

Laura A. Sena, Daniela C. Salles, Elizabeth L. Engle, Qingfeng Zhu, Hanna Tukachinsky, Tamara L. Lotan, Emmanuel S. Antonarakis

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalCold Spring Harbor Molecular Case Studies
Volume7
Issue number4
DOIs
StatePublished - Aug 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was partially supported by the Patrick Walsh Prostate Cancer Research Fund (TLL and ESA), the National Institutes of Health Cancer Center Support Grant P30 CA006973, Department of Defense grants W81XWH-16-PCRP-CCRSA and W81XWH2010079, and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

Funding Information:
ESA is a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Pfizer, Amgen, Lilly, Bayer, AstraZeneca, Bristol-Myers Squibb, Clovis, and Merck; he has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck; and he is the co-inventor of an AR-V7 biomarker technology that has been licensed to Qiagen. TLL has received research funding from Roche, DeepBio and Myriad Genetics. The remaining authors report no conflicts of interest.

Publisher Copyright:
© 2021 Cold Spring Harbor Laboratory Press. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Case Reports

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