Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer
Copyright © 2023. Published by Elsevier Inc..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Cancer cell - 41(2023), 11 vom: 13. Nov., Seite 1972-1988.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hawley, Jessica E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.11.2023 Date Revised 22.11.2023 published: Print-Electronic ClinicalTrials.gov: NCT03951831 Citation Status MEDLINE |
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| doi: |
10.1016/j.ccell.2023.10.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364147628 |
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| 100 | 1 | |a Hawley, Jessica E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 16.11.2023 | ||
| 500 | |a Date Revised 22.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03951831 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Inc. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ADT | |
| 650 | 4 | |a anti-PD-1 therapy | |
| 650 | 4 | |a clinical translational science | |
| 650 | 4 | |a clinical trial | |
| 650 | 4 | |a hormone-sensitive | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a metastatic prostate cancer | |
| 650 | 4 | |a single cell RNA sequencing | |
| 650 | 4 | |a tumor microenvironment | |
| 650 | 7 | |a Androgen Antagonists |2 NLM | |
| 650 | 7 | |a Androgens |2 NLM | |
| 700 | 1 | |a Obradovic, Aleksandar Z |e verfasserin |4 aut | |
| 700 | 1 | |a Dallos, Matthew C |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Emerson A |e verfasserin |4 aut | |
| 700 | 1 | |a Runcie, Karie |e verfasserin |4 aut | |
| 700 | 1 | |a Ager, Casey R |e verfasserin |4 aut | |
| 700 | 1 | |a McKiernan, James |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Christopher B |e verfasserin |4 aut | |
| 700 | 1 | |a Decastro, Guarionex J |e verfasserin |4 aut | |
| 700 | 1 | |a Weintraub, Joshua |e verfasserin |4 aut | |
| 700 | 1 | |a Virk, Renu |e verfasserin |4 aut | |
| 700 | 1 | |a Lowy, Israel |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Chaimowitz, Matthew G |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Xinzheng V |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Haffner, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Worley, Jeremy |e verfasserin |4 aut | |
| 700 | 1 | |a Stein, Mark N |e verfasserin |4 aut | |
| 700 | 1 | |a Califano, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Drake, Charles G |e verfasserin |4 aut | |
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