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Status: Bibliographieeintrag

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Verfasst von:Legscha, Kevin Jan [VerfasserIn]   i
 Ferreira, Edite Antunes [VerfasserIn]   i
 Chamoun, Antonios [VerfasserIn]   i
 Lang, Alexander [VerfasserIn]   i
 Awwad, Mohamed [VerfasserIn]   i
 Ton, Gigi Nu Hoang Quy [VerfasserIn]   i
 Galetzka, Danuta [VerfasserIn]   i
 Guezguez, Borhane [VerfasserIn]   i
 Hundemer, Michael [VerfasserIn]   i
 Bourdon, Jean-Christophe [VerfasserIn]   i
 Munder, Markus [VerfasserIn]   i
 Theobald, Matthias [VerfasserIn]   i
 Echchannaoui, Hakim [VerfasserIn]   i
Titel:Δ133p53α enhances metabolic and cellular fitness of TCR-engineered T cells and promotes superior antitumor immunity
Verf.angabe:Kevin Jan Legscha, Edite Antunes Ferreira, Antonios Chamoun, Alexander Lang, Mohamed Hemaid Sayed Awwad, Gigi Nu Hoang Quy Ton, Danuta Galetzka, Borhane Guezguez, Michael Hundemer, Jean-Christophe Bourdon, Markus Munder, Matthias Theobald, Hakim Echchannaoui
E-Jahr:2021
Jahr:10 June 2021
Umfang:15 S.
Fussnoten:Gesehen am 04.11.2021
Titel Quelle:Enthalten in: Journal for ImmunoTherapy of Cancer
Ort Quelle:London : BioMed Central, 2013
Jahr Quelle:2021
Band/Heft Quelle:9(2021), 6, Artikel-ID e001846, Seite 1-15
ISSN Quelle:2051-1426
Abstract:Background Tumor microenvironment-associated T cell senescence is a key limiting factor for durable effective cancer immunotherapy. A few studies have demonstrated the critical role of the tumor suppressor TP53-derived p53 isoforms in cellular senescence process of non-immune cells. However, their role in lymphocytes, in particular tumor-antigen (TA) specific T cells remain largely unexplored. - Methods Human T cells from peripheral blood were retrovirally engineered to coexpress a TA-specific T cell receptor and the Δ133p53α-isoform, and characterized for their cellular phenotype, metabolic profile and effector functions. - Results Phenotypic analysis of Δ133p53α-modified T cells revealed a marked reduction of the T-cell inhibitory molecules (ie, CD160 and TIGIT), a lower frequency of senescent-like CD57+ and CD160+ CD8+ T cell populations, and an increased number of less differentiated CD28+ T cells. Consistently, we demonstrated changes in the cellular metabolic program toward a quiescent T cell state. On a functional level, Δ133p53α-expressing T cells acquired a long-term proliferative capacity, showed superior cytokine secretion and enhanced tumor-specific killing in vitro and in mouse tumor model. Finally, we demonstrated the capacity of Δ133p53α to restore the antitumor response of senescent T cells isolated from multiple myeloma patients. - Conclusion This study uncovered a broad effect of Δ133p53α isoform in regulating T lymphocyte function. Enhancing fitness and effector functions of senescent T cells by modulation of p53 isoforms could be exploited for future translational research to improve cancer immunotherapy and immunosenescence-related diseases.
DOI:doi:10.1136/jitc-2020-001846
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 ; Verlag: https://doi.org/10.1136/jitc-2020-001846
 Volltext: https://jitc.bmj.com/content/9/6/e001846
 DOI: https://doi.org/10.1136/jitc-2020-001846
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:adoptive
 antigen
 cell engineering
 costimulatory and inhibitory T-cell receptors
 immunotherapy
 receptors
 T-lymphocytes
K10plus-PPN:1776176693
Verknüpfungen:→ Zeitschrift

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