细胞间纳米管介导的线粒体转移增强 T 细胞代谢适应性和抗肿瘤疗效

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.