Cancer Cells Exploit Defective Mitochondria to Weaken Immune Defenses

A groundbreaking study has revealed that cancer cells use defective mitochondria to "poison" immune cells, thereby undermining the body's defense mechanisms and enabling tumors to evade elimination.

Published in the latest issue of Nature, the research provides the strongest evidence to date that mitochondria can migrate not only in cell and animal models but also within the human body.

The research team from Okayama University in Japan analyzed samples from multiple cancer patients, focusing on the mitochondria of cancer cells and tumor-infiltrating lymphocytes (TILs)—immune cells capable of identifying and attacking tumors.

The study found that in some patients, both cancer cells and TILs carried mitochondria with identical mutations. This suggests that mitochondria from cancer cells may migrate into immune cells. To confirm this, researchers genetically engineered cancer cells to tag their mitochondria with fluorescent proteins. When co-cultured with TILs, fluorescently tagged mitochondria were detected inside TILs within just 24 hours. After 15 days, some TILs had their mitochondria almost entirely replaced by those from cancer cells.

Further experiments showed that TILs absorbing cancer-cell mitochondria experienced a significant reduction in their ability to divide and were more prone to entering programmed cell death. In mouse cancer models, TILs that absorbed foreign mitochondria exhibited signs of T-cell exhaustion, losing their capacity to attack cancer cells effectively.

This discovery sheds new light on how cancer cells manipulate immune responses, paving the way for potential therapeutic strategies targeting mitochondrial transfer in cancer treatment.