BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells

Abstract

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. mehr

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Titel	BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells
Medien	Oncoimmunology
Heft	1
Band	11
ISSN	2162-402X
Verfasser	Hannes Forkel, Piotr Grabarczyk, Maren Depke, Sascha Troschke-Meurer, Prof. Dr. 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 Schmidt
Seiten	2148850
Veröffentlichungsdatum	2022
Zitation	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 (2022): BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells. Oncoimmunology 11 (1), 2148850. DOI: 10.1080/2162402X.2022.2148850