Cancer cells have long been known to dodge the body’s immune defenses, allowing tumors to grow and spread. But how they manage to slip past vigilant immune cells and settle in places like lymph nodes has puzzled researchers. A new study reveals a sneaky tactic: cancer cells snatch the powerhouse of the cell, mitochondria, from nearby immune cells, weakening the immune response while boosting their own ability to evade detection and metastasize.
The research, published in Cell Metabolism, draws from experiments in mice, human cell cultures, and analyses of patient tumor samples. It shows that this mitochondrial theft happens across various cancer types, including colon, breast, and melanoma. By taking these organelles, tumor cells not only hobble the immune system’s attack but also trigger internal signals that help them colonize lymph nodes, a key step in cancer’s progression.
Scientists have observed mitochondrial transfer in other contexts, such as between healthy cells to aid repair. In cancer, however, it serves a darker purpose. The study found that tumor cells acquire mitochondria from a broad range of immune cells, including T cells, natural killer cells, and antigen-presenting cells. This process occurs through direct contact, often via thin tunnels called tunneling nanotubes that connect the cells.
Once stolen, the mitochondria fuse with those already in the cancer cells, leading to a leak of mitochondrial DNA into the cell’s cytosol. This leakage activates a pathway known as cGAS-STING, which in turn ramps up type I interferon signaling — a mechanism normally used by cells to fight viruses but here repurposed to help tumors hide from immune surveillance.
Derick Okwan-Duodu et al.
“In cancer cells, the exogenous mitochondria fuse with endogenous mitochondria networks, leak mtDNA into the cytosol, and stimulate cGAS/STING, activating type I interferon-mediated immune evasion programs,” the study authors explain.
The consequences for immune cells are severe. Those that lose mitochondria show reduced ability to present antigens, activate other immune responders, or carry out cytotoxic attacks. For instance, natural killer cells and CD8 T cells exhibit lower levels of key proteins like granzyme B and perforin, which are essential for destroying abnormal cells. This disarmament allows tumor cells to persist and spread more easily.
On the cancer side, the acquired mitochondria enhance traits like proliferation, migration, and invasion. More crucially, they promote expressions of molecules on tumor surfaces, which help shield them from immune elimination in lymph nodes.
“Blocking mitochondrial transfer machinery—including cGAS, STING, or type I interferon—reduced cancer metastasis to the lymph node,” the researchers note.
Citations
Derick Okwan-Duodu et al. Mitochondrial transfer from immune to tumor cells enables lymph node metastasis. Cell Metabolism. Published online January 12, 2026. DOI: 10.1016/j.cmet.2025.12.014
