Transcriptomics

Dataset Information

0

IL-12 Reprograms CAR-Expressing Natural Killer T cells to Long-Lived TH1-Polarized Cells with Potent Antitumor Activity


ABSTRACT: Human natural killer T cells (NKTs) are innate-like T lymphocytes that are increasingly used for cancer immunotherapy. Here we show that human NKTs expressing the pro-inflammatory cytokine interleukin-12 (IL-12) undergo extensive and sustained molecular and functional reprogramming. Specifically, IL-12 instructs and maintain a Th1-polarization program in NKTs in vivo without causing their functional exhaustion. Furthermore, using CD62L as a marker of memory cells in human NKTs, we observed that IL-12 maintains long-term CD62L-expressing memory NKTs in vivo. Notably, IL-12 initiates de novo programming of memory NKTs in CD62L negative NKTs indicating that human NKTs circulating in the peripheral blood possess an intrinsic differentiation hierarchy and that IL-12 plays a role in promoting their differentiation to long-lived Th1-polarized memory cells. Human NKTs engineered to co-express a Chimeric Antigen Receptor (CAR) coupled with the expression of IL-12 showed enhanced antitumor activity in tumor models, persisted long-term in vivo and conserved the molecular signature driven by the IL-12 expression. Thus IL-12 reveals an intrinsic and unappreciated plasticity of peripheral human NKTs that may play a crucial role in the development of cell therapeutics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE241586 | GEO | 2023/11/30

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2022-11-07 | GSE217281 | GEO
2014-08-12 | E-GEOD-54877 | biostudies-arrayexpress
2023-04-19 | GSE223071 | GEO
2023-05-01 | GSE220927 | GEO
2010-06-10 | E-GEOD-8352 | biostudies-arrayexpress
2007-07-07 | GSE8352 | GEO
2009-06-01 | E-MEXP-2153 | biostudies-arrayexpress
2023-02-17 | E-MTAB-12563 | biostudies-arrayexpress
2010-02-17 | E-GEOD-19825 | biostudies-arrayexpress
2015-05-05 | E-GEOD-65627 | biostudies-arrayexpress