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
Organism
Number of Samples 6
Release Date 2024/02/07 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP488614
ENA SRP488614
GEO GSE255244
BioProject PRJNA1074242

Publication

Title
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)
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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