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Verfasst von:Sevko, Alexandra [VerfasserIn]   i
 Michels, Tillmann [VerfasserIn]   i
 Vrohlings, Melissa [VerfasserIn]   i
 Umansky, Ludmila [VerfasserIn]   i
 Beckhove, Philipp [VerfasserIn]   i
 Kato, Masashi [VerfasserIn]   i
 Shurin, Galina V. [VerfasserIn]   i
 Shurin, Michael R. [VerfasserIn]   i
 Umansky, Viktor [VerfasserIn]   i
Titel:Antitumor effect of paclitaxel is mediated by inhibition of myeloid-derived suppressor cells and chronic inflammation in the spontaneous melanoma model
Verf.angabe:Alexandra Sevko, Tillmann Michels, Melissa Vrohlings, Ludmila Umansky, Philipp Beckhove, Masashi Kato, Galina V. Shurin, Michael R. Shurin, and Viktor Umansky
E-Jahr:2013
Jahr:28 January 2013
Umfang:8 S.
Fussnoten:Gesehen am 19.08.2021
Titel Quelle:Enthalten in: The journal of immunology
Ort Quelle:Rockville, Md. : American Association of Immunologists, 1916
Jahr Quelle:2013
Band/Heft Quelle:190(2013), 5, Seite 2464-2471
ISSN Quelle:1550-6606
Abstract:The antitumor effects of paclitaxel are generally attributed to the suppression of microtubule dynamics resulting in defects in cell division. New data demonstrated that in ultralow noncytotoxic concentrations, paclitaxel modulated in immune cells in vitro the activity of small Rho GTPases, the key regulators of intracellular actin dynamics. However, the immunomodulatory properties of paclitaxel in vivo have not been evaluated. In this study, using the ret transgenic murine melanoma model, which mimics human cutaneous melanoma, we tested effects of ultralow noncytotoxic dose paclitaxel on functions of myeloid-derived suppressor cells (MDSCs), chronic inflammatory mediators, and T cell activities in the tumor microenvironment in vivo. Administration of paclitaxel significantly decreased accumulation and immunosuppressive activities of tumor-infiltrating MDSCs without alterations of the bone marrow hematopoiesis. This was associated with the inhibition of p38 MAPK activity, TNF-α and production, and S100A9 expression in MDSCs. The production of mediators of chronic inflammation in the tumor milieu also was diminished. Importantly, reduced tumor burden and increased animal survival upon paclitaxel application was mediated by the restoration of CD8 T cell effector functions. We suggest that the ability of paclitaxel in a noncytotoxic dose to block the immunosuppressive potential of MDSCs in vivo represents a new therapeutic strategy to downregulate immunosuppression and chronic inflammation in the tumor microenvironment for enhancing the efficacy of concomitant anticancer therapies.
DOI:doi:10.4049/jimmunol.1202781
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.

Volltext: https://doi.org/10.4049/jimmunol.1202781
 Volltext: https://www.jimmunol.org/content/190/5/2464
 DOI: https://doi.org/10.4049/jimmunol.1202781
Datenträger:Online-Ressource
Sprache:eng
Bibliogr. Hinweis:Erscheint auch als : Druck-Ausgabe: Antitumor effect of paclitaxel is mediated by inhibition of myeloid-derived suppressor cells and chronic inflammation in the spontaneous melanoma model. - 2013
K10plus-PPN:1767353308
Verknüpfungen:→ Zeitschrift

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