Manru Zhang, Jiaxing Liu, Gen Xu, Hangyu Li, Ying Sun, X.Y. Peng
Mitochondria, an ancient eukaryotic organelle, serve as a primary medium for intercellular communication and material exchange in tumor microenvironments (TME), playing a pivotal role in regulating tumor growth, metastasis, and immune evasion. Researchers have focused particularly on mitochondrial transfer pathways and their subsequent impacts on the TME. This review not only systematically elucidates traditional mitochondrial transfer pathways, such as tunneling nanotubes (TNTs) and extracellular vesicles (EVs), but also further emphasizes emerging mechanisms, particularly mitochondrial transfer mediated by migrasomes and retractosomes. It systematically explores the functional impacts of mitochondrial transfer on tumor immunity and immune therapy resistance. Notably, we discuss the latest advancements in mitochondrial modulation strategies based on CAR-T as potential therapeutic interventions. By integrating these novel perspectives, this review aims to provide updated mechanistic and translational research insights into mitochondrial transfer in cancer biology.