| Autor: |
Forkel, Hannes, Grabarczyk, Piotr, Depke, Maren, Troschke-Meurer, Sascha, Simm, Stefan, Hammer, Elke, Michalik, Stephan, Hentschker, Christian, Corleis, Björn, Loyal, Lucie, Zumpe, Maxi, Siebert, Nikolai, Dorhoi, Anca, Thiel, Andreas, Lode, Holger, Völker, Uwe, Schmidt, Christian A. |
| Předmět: |
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| Zdroj: |
OncoImmunology; 2022, Vol. 11 Issue 1, p1-18, 18p |
| Abstrakt: |
BCL11B, 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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