St et al. 2024 (PRJNA1074242)
General Details
| Title | Ex vivo activation of the GCN2 pathway metabolically reprograms T cells leading to enhanced adoptive cell therapy |
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| Organism | |
| Number of Samples | 6 |
| Release Date | 2024/02/07 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP488614 |
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| ENA | SRP488614 |
| GEO | |
| BioProject | PRJNA1074242 |
Publication
| Title | |
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| Authors | St Paul M,Saibil SD,Kates M,Han S,Lien SC,Laister RC,Hezaveh K,Kloetgen A,Penny S,Guo T,Garcia-Batres C,Smith LK,Chung DC,Elford AR,Sayad A,Pinto D,Mak TW,Hirano N,McGaha T,Ohashi PS |
| Journal | Cell reports. Medicine |
| Publication Date | 2024 Mar 19 |
| Abstract | The manipulation of T cell metabolism to enhance anti-tumor activity is an area of active investigation. Here, we report that activating the amino acid starvation response in effector CD8 + T cells ex vivo using the general control non-depressible 2 (GCN2) agonist halofuginone (halo) enhances oxidative metabolism and effector function. Mechanistically, we identified autophagy coupled with the CD98-mTOR axis as key downstream mediators of the phenotype induced by halo treatment. The adoptive transfer of halo-treated CD8 + T cells into tumor-bearing mice led to robust tumor control and curative responses. Halo-treated T cells synergized in vivo with a 4-1BB agonistic antibody to control tumor growth in a mouse model resistant to immunotherapy. Importantly, treatment of human CD8 + T cells with halo resulted in similar metabolic and functional reprogramming. These findings demonstrate that activating the amino acid starvation response with the GCN2 agonist halo can enhance T cell metabolism and anti-tumor activity. Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved. |
| PMC | PMC10983112 |
| PMID | 38460518 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR27899688 | PRJNA1074242 | Mus musculus | CD8+ T cells | Ribo-Seq |  |
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| SRR27899687 | PRJNA1074242 | Mus musculus | CD8+ T cells | Ribo-Seq | |
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| SRR27899686 | PRJNA1074242 | Mus musculus | CD8+ T cells | Ribo-Seq | |
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| SRR27899685 | PRJNA1074242 | Mus musculus | CD8+ T cells | Ribo-Seq | |
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| SRR27899684 | PRJNA1074242 | Mus musculus | CD8+ T cells | Ribo-Seq | |
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| SRR27899683 | PRJNA1074242 | Mus musculus | CD8+ T cells | Ribo-Seq | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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