[Mitochondria in Cancer and Immunity]

Mitochondria are multifunctional organelles responsible not only for ATP production via oxidative phosphorylation but also for a wide range of cellular activities, including biosynthesis, redox regulation, signal transduction, and the control of apoptosis. In both cancer and immune cells, mitochondrial function plays various roles that extend beyond mere energy production. While cancer cells are known for the Warburg effect‒an enhanced glycolysis even in the presence of oxygen-they also actively utilize mitochondrial metabolism to fuel tumor progression. Furthermore, mutations in mitochondrial DNA(mtDNA) and alterations in nuclear genes encoding mitochondrial proteins contribute to tumorigenesis through various mechanisms, such as epigenetic modifications and the evasion of apoptosis. In immune cells, such as T cells and macrophages, mitochondrial metabolism is crucial for their differentiation and functional regulation. Key processes such as T cell activation, memory formation, and exhaustion, as well as macrophage functional polarization and inflammatory responses, are tightly linked to mitochondrial functional states. Recently, intercellular mitochondrial transfer within the tumor microenvironment has emerged as a significant phenomenon. Cancer cells can acquire mitochondria from surrounding cells to enhance their metabolic capacity and therapeutic resistance. Conversely, the transfer of mitochondria from cancer cells to T cells has been shown to suppress antitumor immune responses through metabolic dysfunction and homoplasmic replacement of T cell mtDNA. Based on these findings, therapeutic strategies targeting mitochondria are under investigation. These include inhibiting mitochondrial metabolism in cancer cells, boosting mitochondrial metabolism in T cells, and blocking intercellular mitochondrial transfer. Although preclinical studies have yielded promising results, further research is necessary to establish effective clinical therapies that can precisely modulate the complex metabolic interplay between cancer and immune cells.