Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer.

Autor:	Hawley JE; Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Obradovic AZ; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA., Dallos MC; Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Lim EA; Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Runcie K; Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Ager CR; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA., McKiernan J; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA., Anderson CB; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA., Decastro GJ; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA., Weintraub J; Department of Interventional Radiology, Columbia University Irving Medical Center, New York, NY, USA., Virk R; Department of Pathology, Columbia University Irving Medical Center, New York, NY, USA., Lowy I; Regeneron Pharmaceuticals, Tarrytown, NY, USA., Hu J; Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA., Chaimowitz MG; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA., Guo XV; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA., Zhang Y; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA., Haffner MC; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA; Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA, USA., Worley J; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA., Stein MN; Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA., Califano A; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biochemistry & Molecular Biophysics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032 USA; Department of Biomedical Informatics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032 USA; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032 USA; J.P. Sulzberger Columbia Genome Center, Columbia University Irving Medical Center, New York, NY 10032 USA. Electronic address: ac2248@cumc.columbia.edu., Drake CG; Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA; Department of Interventional Radiology, Columbia University Irving Medical Center, New York, NY, USA. Electronic address: cgd2139@columbia.edu.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2023 Nov 13; Vol. 41 (11), pp. 1972-1988.e5. Date of Electronic Publication: 2023 Nov 02.
DOI:	10.1016/j.ccell.2023.10.006
Abstrakt:	When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy. We perform a longitudinal, protein activity-based analysis of TME subpopulations, revealing immune subpopulations conserved across multiple metastatic sites. We also observe dynamic changes in these immune subpopulations in response to treatment and a correlation with clinical outcomes. Our study uncovers a therapy-resistant, transcriptionally distinct tumor subpopulation that expands in cell number in treatment-refractory patients. Competing Interests: Declaration of interests Dr. Hawley has served as a paid consultant to Seagen, Daiichi Sankyo, and ImmunityBio and has received sponsored research funding to her institution from Astra Zeneca, Bristol Meyers Squibb, Crescendo Biologics, Macrogenics, and Vaccitech. Dr. Drake is a co-inventor on patents licensed from JHU to BMS and Janssen and is currently an employee of Janssen Research. Dr. Califano is founder, equity holder, and consultant of DarwinHealth Inc., a company that has licensed some of the algorithms used in this manuscript from Columbia University. Columbia University is also an equity holder in DarwinHealth Inc. Dr. Lowy is an employee and stockholder of Regeneron Pharmaceuticals. (Copyright © 2023. Published by Elsevier Inc.)
Databáze:	MEDLINE
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