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| Status |
Public on Apr 01, 2021 |
| Title |
Metabolic Reprogramming of Terminally Exhausted CD8+ T-cells by Interleukin-10 Enhances Anti-Tumour Immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Terminally exhausted CD8+ T-cells, which hold certain level of anti-tumour cytotoxicity but largely reduced proliferation capacity, contribute directly to tumour growth control. However, this subpopulation do not respond to immune checkpoint blockades or most existing immunotherapies and are difficult to be reactivated. Here, we show that a half-life extended interleukin (IL)-10/Fc fusion protein directly expands the terminally exhausted CD8+ TILs and sustains their effector functions through in vivo metabolic reprogramming, leading to eradication of established solid tumours and durable cures in a majority of treated mice when combined with adoptive T-cell transfer immunotherapy. Our results provide preclinical evidence that IL-10/Fc is a safe and highly effective therapy that acts on a specific subset of CD8+ TILs distinct from those responding to immune checkpoint blockades. Thus, IL-10/Fc could complement and synergize with existing cancer immunotherapies for enhanced efficacy and response rates. We find that IL-10/Fc reprograms T-cell metabolism by promoting oxidative phosphorylation through the mitochondrial pyruvate carrier, suggesting that metabolic reprogramming is sufficient to revitalize terminally exhausted CD8+ TILs.
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| Overall design |
The goals of this study are to use NGS to perform transcriptome profiling (RNA-seq) to find the changes of the global gene expression programs of tumor-infiltrating terminally exhausted CD8+ T-cells from IL-10/Fc treated mice. PBS treated mice were used as controls. Total RNA was extracted and submitted to RNA-seq
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| Web link |
https://www.nature.com/articles/s41590-021-00940-2
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| Contributor(s) |
Guo Y, Xie Y, Tang L |
| Citation(s) |
34031618 |
| |
| Submission date |
Mar 16, 2021 |
| Last update date |
Jul 01, 2021 |
| Contact name |
Li Tang |
| Organization name |
École polytechnique fédérale de Lausanne (EPFL)
|
| Department |
Institute of Bioengineering (IBI) / Institute of Materials (IMX)
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| Lab |
Laboratory of Biomaterials for Immunoengineering (LBI)
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| Street address |
MED 1 2826, Station 9, CH-1015 Lausanne
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| City |
Lausanne |
| State/province |
Vaud |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA714871 |
| SRA |
SRP310862 |
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