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

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 exhib

SUBMITTER: Baldwin JG 

PROVIDER: S-EPMC11623344 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature