Back to Search
Start Over
Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment.
- Source :
-
Cancer cell [Cancer Cell] 2021 Nov 08; Vol. 39 (11), pp. 1464-1478.e8. Date of Electronic Publication: 2021 Oct 15. - Publication Year :
- 2021
-
Abstract
- Bone metastases are devastating complications of cancer. They are particularly common in prostate cancer (PCa), represent incurable disease, and are refractory to immunotherapy. We seek to define distinct features of the bone marrow (BM) microenvironment by analyzing single cells from bone metastatic prostate tumors, involved BM, uninvolved BM, and BM from cancer-free, orthopedic patients, and healthy individuals. Metastatic PCa is associated with multifaceted immune distortion, specifically exhaustion of distinct T cell subsets, appearance of macrophages with states specific to PCa bone metastases. The chemokine CCL20 is notably overexpressed by myeloid cells, as is its cognate CCR6 receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic PCa bone metastases restores T cell reactivity and significantly prolongs animal survival. Comparative high-resolution analysis of PCa bone metastases shows a targeted approach for relieving local immunosuppression for therapeutic effect.<br />Competing Interests: Declaration of interests P.V.K. serves on the Scientific Advisory Board to Celsius Therapeutics Inc. and Biomage Inc. D.T.S. is a director and shareholder for Agios Therapeutics and Editas Medicines; a founder, director, shareholder, and scientific advisory board member for Magenta Therapeutics and LifeVault Bio, a shareholder and founder of Fate Therapeutics, and a director, founder, and shareholder for Clear Creek Bio, a consultant for FOG Pharma and VCanBio, and a recipient of sponsored research funding from Novartis. D.B.S. is a founder, consultant, and shareholder for Clear Creek Bio.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Bone Neoplasms genetics
Bone Neoplasms immunology
Case-Control Studies
Cell Line, Tumor
Chemokine CCL20 metabolism
Gene Expression Regulation, Neoplastic
Humans
Macrophages immunology
Male
Mice
Myeloid Cells immunology
Prostatic Neoplasms genetics
Prostatic Neoplasms immunology
Receptors, CCR6 metabolism
Single-Cell Analysis
T-Lymphocytes immunology
Tumor Microenvironment
Bone Neoplasms pathology
Bone Neoplasms secondary
Chemokine CCL20 genetics
Prostatic Neoplasms pathology
Receptors, CCR6 genetics
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 39
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 34719426
- Full Text :
- https://doi.org/10.1016/j.ccell.2021.09.005