BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells
| Autor: | Hannes Forkel, Piotr Grabarczyk, Maren Depke, Sascha Troschke-Meurer, Stefan Simm, Elke Hammer, Stephan Michalik, Christian Hentschker, Björn Corleis, Lucie Loyal, Maxi Zumpe, Nikolai Siebert, Anca Dorhoi, Andreas Thiel, Holger Lode, Uwe Völker, Christian A. Schmidt |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | OncoImmunology, Vol 11, Iss 1 (2022) |
| Druh dokumentu: | article |
| ISSN: | 2162402X 2162-402X |
| DOI: | 10.1080/2162402X.2022.2148850 |
| Popis: | ABSTRACTBCL11B, an essential transcription factor for thymopoiesis, regulates also vital processes in post-thymic lymphocytes. Increased expression of BCL11B was recently correlated with the maturation of NK cells, whereas reduced BCL11B levels were observed in native and induced T cell subsets displaying NK cell features. We show that BCL11B-depleted CD8+ T cells stimulated with IL-15 acquired remarkable innate characteristics. These induced innate CD8+ (iiT8) cells expressed multiple innate receptors like NKp30, CD161, and CD16 as well as factors regulating migration and tissue homing while maintaining their T cell phenotype. The iiT8 cells effectively killed leukemic cells spontaneously and neuroblastoma spheroids in the presence of a tumor-specific monoclonal antibody mediated by CD16 receptor activation. These iiT8 cells integrate the innate natural killer cell activity with adaptive T cell longevity, promising an interesting therapeutic potential. Our study demonstrates that innate T cells, albeit of limited clinical applicability given their low frequency, can be efficiently generated from peripheral blood and applied for adoptive transfer, CAR therapy, or combined with therapeutic antibodies. |
| Databáze: | Directory of Open Access Journals |
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