| Online-Ressource |
Verfasst von: | Legscha, Kevin Jan [VerfasserIn]  |
| Ferreira, Edite Antunes [VerfasserIn]  |
| Chamoun, Antonios [VerfasserIn]  |
| Lang, Alexander [VerfasserIn]  |
| Awwad, Mohamed [VerfasserIn]  |
| Ton, Gigi Nu Hoang Quy [VerfasserIn]  |
| Galetzka, Danuta [VerfasserIn]  |
| Guezguez, Borhane [VerfasserIn]  |
| Hundemer, Michael [VerfasserIn]  |
| Bourdon, Jean-Christophe [VerfasserIn]  |
| Munder, Markus [VerfasserIn]  |
| Theobald, Matthias [VerfasserIn]  |
| Echchannaoui, Hakim [VerfasserIn]  |
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 |
Δ133p53α enhances metabolic and cellular fitness of TCR-engineered T cells and promotes superior antitumor immunity / Legscha, Kevin Jan [VerfasserIn]; 10 June 2021 (Online-Ressource)