Reversible mitochondrial dysfunction drives terminal T-cell exhaustion
UID: 10953
- Description
- Summary from GEO:
"The failure of T-cells to control tumor growth has been associated with several functional defects that collectively lead to T-cell “exhaustion.” This phenotype results from chronic antigen stimulation within the tumor microenvironment, but how repetitive antigenic stimulation leads to T-cell exhaustion remains poorly defined. Here we show that persistent antigen stimulation induces mitochondrial oxidative stress that reduces tricarboxylic acid (TCA) cycle activity. The resultant bioenergetic compromise impairs nucleotide triphosphate synthesis, induces endoplasmic reticulum (ER) stress, and activates an exhaustion-associated gene expression program. Reversal of oxidative stress with N-acetylcysteine effectively restores T-cell proliferation, effector function, and memory-associated gene expression and enhances anti-tumor T-cell efficacy in vivo. These data reveal that induction of mitochondrial oxidative stress is a critical component of terminal T-cell dysfunction. Furthermore, treatments that restore mitochondrial redox are sufficient to prevent T-cell exhaustion and enhance anti-tumor immunity."
Overall design from GEO:
"RNA-sequencing of polyclonal or OT-I transgenic CD8+ T cells following acute or chronic TCR stimulation ex vivo, +/- N-acetylcysteine."
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Access via GEO
Accession #: GSE138459Access via BioProject
Accession #: PRJNA575910Access via SRA
Accession #: SRP224398 - Access Restrictions
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Free to All
- Access Instructions
- The NCBI Gene Expression Omnibus, SRA and BioProject databases provide open access to these files.
- Associated Publications
- Equipment Used
- Dataset Format(s)
- TXT
- Dataset Size
- 2.2 MB
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