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Intercellular nanotube-mediated mitochondrial transfer enhances T-cell metabolic fitness and antitumor efficacy

GSE229487 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2024/09/13 Platform GPL24247
Summary
Mitochondrial loss and dysfunction drive T cell exhaustion and represent major barriers to successful T cell immunotherapies. We found that mesenchymal stromal cells (MSC) establish nanotubular connections with T cells in a TLN2-dependent manner and leveraged these intercellular highways to supply new mitochondria to CD8+ T cells. Acquisition of MSC mitochondria increased T cell basal mitochondrial respiration and spare respiratory capacity. When transferred into tumor-bearing hosts, tumor-specific CD8+ T cells with donated mitochondria expanded more robustly, infiltrated the tumor more efficiently, and exhibited fewer signs of exhaustion compared to CD8+ T cells that did not take up mitochondria. As a result, mitochondria-boosted CD8+ T cells mediated superior antitumor responses, prolonging animal survival. To unravel the mechanisms behind mitochondrial transfer we performed RNA sequencing on CD8+ T cells that acquired donor mitochondria (MitoPositive), or did not acquire donor mitochondira (MitoNegative) directly after after co-culture (0hr timepoint).
Published in
Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy
Baldwin JG, Heuser-Loy C, Saha T et al. · Cell 2024 · PMID 39276774 · doi:10.1016/j.cell.2024.08.029
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Also filed as BioProject PRJNA954743 and SRA study SRP432195. Searching any of these in the dataset finder brings you back here.

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