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 | GSE255244 |
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 | NA_CD8+ T cells | Ribo-Seq | 0.0 | ||||||||
SRR27899687 | PRJNA1074242 | Mus musculus | NA_CD8+ T cells | Ribo-Seq | 0.0 | ||||||||
SRR27899686 | PRJNA1074242 | Mus musculus | NA_CD8+ T cells | Ribo-Seq | 0.0 | ||||||||
SRR27899685 | PRJNA1074242 | Mus musculus | NA_CD8+ T cells | Ribo-Seq | 0.0 | ||||||||
SRR27899684 | PRJNA1074242 | Mus musculus | NA_CD8+ T cells | Ribo-Seq | 0.0 | ||||||||
SRR27899683 | PRJNA1074242 | Mus musculus | NA_CD8+ T cells | Ribo-Seq | 0.0 | ||||||||
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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