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BCL11B depletion induces the development of highly cytotoxic innate T cells out of IL-15 stimulated peripheral blood αβ CD8+ T cells
- 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.
Author: | Hannes Forkel, Piotr Grabarczyk, Maren Depke, Sascha Troschke-Meurer, Stefan Simm, Elke HammerORCiD, Stephan Michalik, Christian Hentschker, Björn Corleis, Lucie Loyal, Maxi Zumpe, Nikolai Siebert, Anca Dorhoi, Andreas Thiel, Holger N. LodeORCiD, Uwe VölkerORCiD, Christian A. Schmidt |
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URN: | urn:nbn:de:gbv:9-opus-105241 |
DOI: | https://doi.org/10.1080/2162402X.2022.2148850 |
ISSN: | 2162-402X |
Parent Title (English): | OncoImmunology |
Publisher: | Taylor & Francis |
Place of publication: | London |
Document Type: | Article |
Language: | English |
Date of first Publication: | 2022/12/05 |
Release Date: | 2024/01/22 |
Tag: | ADCC; AICC; BCL11B; CRISPR/Cas; IL-15; alpha- beta CD8+ T cells; human; innateness; knock-out |
Volume: | 11 |
Issue: | 1 |
Article Number: | e2148850 |
Page Number: | 18 |
Faculties: | Universitätsmedizin / Kliniken und Polikliniken für Innere Medizin |
Collections: | Artikel aus DFG-gefördertem Publikationsfonds |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell |