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| Verfasst von: | Balta, Emre [VerfasserIn]  |
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| | Janzen, Nina [VerfasserIn] |
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| | Kirchgessner, Henning [VerfasserIn] |
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| | Toufaki, Vasiliki [VerfasserIn] |
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| | Orlik, Christian [VerfasserIn] |
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| | Liang, Jie [VerfasserIn] |
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| | Lairikyengbam, Divya [VerfasserIn] |
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| | Abken, Hinrich [VerfasserIn] |
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| | Niesler, Beate [VerfasserIn] |
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| | Müller-Decker, Karin [VerfasserIn] |
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| | Ruppert, Thomas [VerfasserIn] |
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| | Samstag, Yvonne [VerfasserIn] |
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| Titel: | Expression of TRX1 optimizes the antitumor functions of human CAR T cells and confers resistance to a pro-oxidative tumor microenvironment |
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| Verf.angabe: | Emre Balta, Nina Janzen, Henning Kirchgessner, Vasiliki Toufaki, Christian Orlik, Jie Liang, Divya Lairikyengbam, Hinrich Abken, Beate Niesler, Karin Müller-Decker, Thomas Ruppert and Yvonne Samstag |
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| E-Jahr: | 2022 |
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| Jahr: | 14 December 2022 |
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| Umfang: | 19 S. |
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| Fussnoten: | Gesehen am 23.01.2023 |
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| Titel Quelle: | Enthalten in: Frontiers in immunology |
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| Ort Quelle: | Lausanne : Frontiers Media, 2010 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 13(2022), Artikel-ID 1063313, Seite 1-19 |
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| ISSN Quelle: | 1664-3224 |
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| Abstract: | Use of chimeric antigen receptor (CAR) T cells to treat B cell lymphoma and leukemia has been remarkably successful. Unfortunately, the therapeutic efficacy of CAR T cells against solid tumors is very limited, with immunosuppression by the pro-oxidative tumor microenvironment (TME) a major contributing factor. High levels of reactive oxygen species are well-tolerated by tumor cells due to their elevated expression of antioxidant proteins; however, this is not the case for T cells, which consequently become hypo-responsive. The aim of this study was to improve CAR T cell efficacy in solid tumors by empowering the antioxidant capacity of CAR T cells against the pro-oxidative TME. To this end, HER2-specific human CAR T cells stably expressing two antioxidant systems: thioredoxin-1 (TRX1), and glutaredoxin-1 (GRX1) were generated and characterized. Thereafter, antitumor functions of CAR T cells were evaluated under control or pro-oxidative conditions. To provide insights into the role of antioxidant systems, gene expression profiles as well as global protein oxidation were analyzed. Our results highlight that TRX1 is pivotal for T cell redox homeostasis. TRX1 expression allows CAR T cells to retain their cytolytic immune synapse formation, cytokine release, proliferation, and tumor cell-killing properties under pro-oxidative conditions. Evaluation of differentially expressed genes and the first comprehensive redoxosome analysis of T cells by mass spectrometry further clarified the underlying mechanisms. Taken together, enhancement of the key antioxidant TRX1 in human T cells opens possibilities to increase the efficacy of CAR T cell treatment against solid tumors. |
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| DOI: | doi:10.3389/fimmu.2022.1063313 |
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| URL: | kostenfrei: Volltext: https://doi.org/10.3389/fimmu.2022.1063313 |
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| | kostenfrei: Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1063313 |
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| | DOI: https://doi.org/10.3389/fimmu.2022.1063313 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 183179960X |
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| Verknüpfungen: | → Zeitschrift |
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| Lokale URL UB: |  Zum Volltext |
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Expression of TRX1 optimizes the antitumor functions of human CAR T cells and confers resistance to a pro-oxidative tumor microenvironment / Balta, Emre [VerfasserIn]; 14 December 2022 (Online-Ressource)
