Baldwin, Jeremy G. and Heuser-Loy, Christoph and Saha, Tanmoy and Schelker, Roland C. and Slavkovic-Lukic, Dragana and Strieder, Nicholas and Hernandez-Lopez, Inmaculada and Rana, Nisha and Barden, Markus and Mastrogiovanni, Fabio and Martin-Santos, Azucena and Raimondi, Andrea and Brohawn, Philip and Higgs, Brandon W. and Gebhard, Claudia and Kapoor, Veena and Telford, William G. and Gautam, Sanjivan and Xydia, Maria and Beckhove, Philipp and Frischholz, Sina and Schober, Kilian and Kontarakis, Zacharias and Corn, Jacob E. and Iannacone, Matteo and Inverso, Donato and Rehli, Michael and Fioravanti, Jessica and Sengupta, Shiladitya and Gattinoni, Luca (2024) Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy. CELL, 187 (23). 6614-6630.e21. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)Abstract
Mitochondrial loss and dysfunction drive T cell exhaustion, representing major barriers to successful T cell-based immunotherapies. Here, we describe an innovative platform to supply exogenous mitochondria to T cells, overcoming these limitations. We found that bone marrow stromal cells establish nanotubular connections with T cells and leverage these intercellular highways to transplant stromal cell mitochondria into CD8(+) T cells. Optimal mitochondrial transfer required Talin 2 on both donor and recipient cells. CD8(+) T cells with donated mitochondria displayed enhanced mitochondrial respiration and spare respiratory capacity. When transferred into tumor-bearing hosts, these supercharged T cells expanded more robustly, infiltrated the tumor more efficiently, and exhibited fewer signs of exhaustion compared with T cells that did not take up mitochondria. As a result, mitochondria-boosted CD8(+) T cells mediated superior antitumor responses, prolonging animal survival. These findings establish intercellular mitochondrial transfer as a prototype of organelle medicine, opening avenues to next-generation cell therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STROMAL CELLS; STEM-CELLS; CANCER; CHEMOTHERAPY; MECHANISM; HEALTH |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jan 2026 06:36 |
| Last Modified: | 27 Jan 2026 06:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64296 |
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