Dokument: Unleashing T cell anti-tumor immunity: new potential for 5-Nonloxytryptamine as an agent mediating MHC-I upregulation in tumors
| Titel: | Unleashing T cell anti-tumor immunity: new potential for 5-Nonloxytryptamine as an agent mediating MHC-I upregulation in tumors | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67506 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20241114-101835-1 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Stachura, Pawel [Autor] Liu, Wei [Autor] Xu, Haifeng C. [Autor] Wlodarczyk, Agnès [Autor] Stencel, Olivia [Autor] Pandey, Piyush [Autor] Vogt, Melina [Autor] Bhatia, Sanil [Autor] Picard, Danniel [Autor] Remke, Marc [Autor] | |||||||
| Dateien: |
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| Stichwörter: | cAMP response element-binding protein (CREB), Antigen-presenting machinery, Immunotherapy, CD8+ T cells, 5-Nonyloxytryptamine (5-NL), Cold tumors | |||||||
| Beschreibung: | Background
New therapies are urgently needed in melanoma, particularly in late-stage patients not responsive to immunotherapies and kinase inhibitors. To uncover novel potentiators of T cell anti-tumor immunity, we carried out an ex vivo pharmacological screen and identified 5-Nonyloxytryptamine (5-NL), a serotonin agonist, as increasing the ability of T cells to target tumor cells. Methods The pharmacological screen utilized lymphocytic choriomeningitis virus (LCMV)-primed splenic T cells and melanoma B16.F10 cells expressing the LCMV gp33 CTL epitope. In vivo tumor growth in C57BL/6 J and NSG mice, in vivo antibody depletion, flow cytometry, immunoblot, CRISPR/Cas9 knockout, histological and RNA-Seq analyses were used to decipher 5-NL’s immunomodulatory effects in vitro and in vivo. Results 5-NL delayed tumor growth in vivo and the phenotype was dependent on the hosts’ immune system, specifically CD8+T cells. 5-NL’s pro-immune effects were not directly consequential to T cells. Rather, 5-NL upregulated antigen presenting machinery in melanoma and other tumor cells in vitro and in vivo without increasing PD-L1 expression. Mechanistic studies indicated that 5-NL’s induced MHC-I expression was inhibited by pharmacologically preventing cAMP Response Element-Binding Protein (CREB) phosphorylation. Importantly, 5-NL combined with anti-PD1 therapy showed significant improvement when compared to single anti-PD-1 treatment. Conclusions This study demonstrates novel therapeutic opportunities for augmenting immune responses in poorly immunogenic tumors. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Stachura, P., Liu, W., Xu, H. C., Wlodarczyk, A., Stencel, O., Pandey, P., Vogt, M., Bhatia, S., Picard, D., Remke, M., Lang, K. S., Häussinger, D., Homey, B., Lang, P. A., Borkhardt, A., & Pandyra, A. A. (2023). Unleashing T cell anti-tumor immunity: new potential for 5-Nonloxytryptamine as an agent mediating MHC-I upregulation in tumors. Molecular Cancer, 22(1), Article 136. https://doi.org/10.1186/s12943-023-01833-8 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 14.11.2024 | |||||||
| Dateien geändert am: | 14.11.2024 |
