| |  Online-Ressource |
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| Verfasst von: | Martins, Christina [VerfasserIn]  |
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| | Rasbach, Erik [VerfasserIn] |
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| | Heppt, Markus V. [VerfasserIn] |
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| | Singh, Praveen [VerfasserIn] |
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| | Kulcsar, Zsofi [VerfasserIn] |
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| | Holzgruber, Julia [VerfasserIn] |
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| | Chakraborty, Asmi [VerfasserIn] |
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| | Mucciarone, Kyla [VerfasserIn] |
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| | Kleffel, Sonja [VerfasserIn] |
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| | Brandenburg, Anne [VerfasserIn] |
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| | Hoetzenecker, Wolfram [VerfasserIn] |
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| | Rahbari, Nuh Nabi [VerfasserIn] |
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| | DeCaprio, James A. [VerfasserIn] |
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| | Thakuria, Manisha [VerfasserIn] |
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| | Murphy, George F. [VerfasserIn] |
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| | Ramsey, Matthew R. [VerfasserIn] |
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| | Posch, Christian [VerfasserIn] |
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| | Barthel, Steven R. [VerfasserIn] |
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| | Schatton, Tobias [VerfasserIn] |
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| Titel: | Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling |
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| Verf.angabe: | Christina Martins, Erik Rasbach, Markus V. Heppt, Praveen Singh, Zsofi Kulcsar, Julia Holzgruber, Asmi Chakraborty, Kyla Mucciarone, Sonja Kleffel, Anne Brandenburg, Wolfram Hoetzenecker, Nuh N. Rahbari, James A. DeCaprio, Manisha Thakuria, George F. Murphy, Matthew R. Ramsey, Christian Posch, Steven R. Barthel, Tobias Schatton |
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| E-Jahr: | 2024 |
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| Jahr: | Jan 2024 |
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| Umfang: | 16 S. |
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| Fussnoten: | Veröffentlicht: 19. Januar 2024 ; Gesehen am 01.08.2024 |
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| Titel Quelle: | Enthalten in: Science advances |
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| Ort Quelle: | Washington, DC [u.a.] : Assoc., 2015 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 10(2024), 3 vom: Jan., Artikel-ID eadi2012, Seite 1-16 |
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| ISSN Quelle: | 2375-2548 |
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| Abstract: | Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Inhibitors targeting the programmed cell death 1 (PD-1) immune checkpoint have improved MCC patient outcomes by boosting antitumor T cell immunity. Here, we identify PD-1 as a growth-promoting receptor intrinsic to MCC cells. In human MCC lines and clinical tumors, RT-PCR-based sequencing, immunoblotting, flow cytometry, and immunofluorescence analyses demonstrated PD-1 gene and protein expression by MCC cells. MCC-PD-1 ligation enhanced, and its inhibition or silencing suppressed, in vitro proliferation and in vivo tumor xenograft growth. Consistently, MCC-PD-1 binding to PD-L1 or PD-L2 induced, while antibody-mediated PD-1 blockade inhibited, protumorigenic mTOR signaling, mitochondrial (mt) respiration, and ROS generation. Last, pharmacologic inhibition of mTOR or mtROS reversed MCC-PD-1:PD-L1-dependent proliferation and synergized with PD-1 checkpoint blockade in suppressing tumorigenesis. Our results identify an MCC-PD-1-mTOR-mtROS axis as a tumor growth-accelerating mechanism, the blockade of which might contribute to clinical response in patients with MCC. |
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| DOI: | doi:10.1126/sciadv.adi2012 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1126/sciadv.adi2012 |
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| | kostenfrei: Volltext: https://www.science.org/doi/10.1126/sciadv.adi2012 |
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| | DOI: https://doi.org/10.1126/sciadv.adi2012 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1897346263 |
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| Verknüpfungen: | → Zeitschrift |
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Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling / Martins, Christina [VerfasserIn]; Jan 2024 (Online-Ressource)
