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| Status |
Public on Oct 19, 2018 |
| Title |
Antioxidant metabolism in activated CD8+ T cells regulates stem-like human memory T cell formation and anti-tumor immunity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Adoptive T cell transfer (ACT) immunotherapy benefits from early-differentiated memory stem-like T (TSCM) cells capable to persist in the long term and to generate potent anti-tumor effectors. Due to their paucity ex vivo, TSCM can be derived from less differentiated naïve precursors but the molecular signals at the basis of their generation are ill-defined. We found that less differentiated human circulating CD8+ T cells display substantial antioxidant capacity ex vivo compared to more differentiated central and effector memory T cells. Limiting reactive oxygen species (ROS) metabolism with anti-oxidants during naïve T cell activation hindered terminal differentiation while allowing expansion and generation of TSCM cells. N-acetylcysteine, the most effective in this regard, induced a transcriptional network and a metabolic profile characteristic of self-renewing memory T cells. Upon ACT, the generated TSCM cells established long-term immunity in vivo and exerted more potent anti-tumor immunity in a xenogeneic model when redirected with CD19 CAR, highlighting the translational relevance of NAC as a simple and inexpensive method to improve ACT
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| |
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| Overall design |
mRNA profiles of human CD8 T cells after 8 days of cell culture with or without N-acetyl cysteine (NAC)
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| |
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| Contributor(s) |
Pilipow K, Scamardella E, Puccio S, Mazza EM, Gattinoni L, Lugli E |
| Citation(s) |
30232291 |
| |
| Submission date |
May 22, 2018 |
| Last update date |
Mar 26, 2019 |
| Contact name |
Emilia Maria Cristina Mazza |
| E-mail(s) |
Emilia.Mazza@humanitasresearch.it
|
| Organization name |
Humanitas Clinical and Research Center
|
| Street address |
Via Alessandro Manzoni, 56
|
| City |
Rozzano, Milan |
| ZIP/Postal code |
20089 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (12)
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| Relations |
| BioProject |
PRJNA472586 |
| SRA |
SRP148680 |
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