Intercellular mitochondrial transfer has emerged as a significant mode of communication within the tumor microenvironment (TME). We propose that this process operates as a stress-adaptive organelle economy, redistributing three biologically decisive assets (respiratory competence, redox tolerance, and stress history) among tumor, immune, and stromal cells according to local metabolic asymmetry. Cancer cells acquire healthy mitochondria from stromal and immune populations, thereby restoring oxidative phosphorylation, expanding metabolic plasticity, and driving chemoresistance. Tumor cells also engage in outward transfer that is recipient-selective. Damaged mitochondria may be exported to CD8 + T cells and fibroblasts, corrupting effector function and reprogramming the stroma, whereas functional mitochondria may be delivered to pro-tumor immune populations such as M2 tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells to sustain their immunosuppressive activity. Functional mitochondria therefore play a dual role in tumorigenesis. The consequences for antitumor immunity depend on donor identity, cargo quality, and recipient lineage rather than on transfer itself. The principal transport routes are tunneling nanotubes, extracellular vesicles, and cell fusion, but biological outcome is ultimately governed by a post-transfer fate checkpoint involving PINK1/Parkin-mediated mitophagy and USP30-facilitated retention. Therapeutically, the goal is not to block or enhance transfer globally but to achieve context-selective modulation within an inherently bidirectional system.
Xu et al. (Wed,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: