Cancer may evade immune defenses by hijacking mitochondria

Cancer cells use mitochondria stolen from immune cells to spread and escape detection, according to a study published this week in the journal Cell metabolism¹.

Scientists have struggled to fully explain how some cancer cells spread to and survive in lymph nodes, which are full of cells that should be able to kill them.

A new type of mitochondria

Derek Okwan-Dodo, an immunologist and clinical pathologist at Stanford University in California, looked for answers in the emerging field of mitochondrial transport, where tiny cellular energy factories known as mitochondria move from one cell to another.

Okwan-Dodo and colleagues found that cancer cells transplanted into mice acquired mitochondria from a variety of immune cells. They did so at equal rates regardless of whether they were implanted in a lymph node or skin.

Stolen batteries

This mitochondrial theft appears to have at least two effects that benefit cancer cells. Not only did this weaken the immune cells from which these powerful organelles had been stolen, it also triggered a beneficial molecular pathway in the cancer cells that had acquired them.

Cancer cells that took up mitochondria began to express genes related to the type I interferon pathway, an immune signaling cascade that may help cells evade the immune system and support lymph node invasion. Okwan-Dodo and colleagues found that silencing genes associated with this pathway reduced the ability of cancer cells to migrate to lymph nodes in mice.

The findings represent “an entirely new mechanism by which mitochondrial transport helps cancer progress,” says Cynthia Reinhart King, a bioengineer at Rice University in Houston, Texas.

The benefits to cancer cells remained even when the researchers destroyed the stolen mitochondria’s ability to produce the energy-carrying molecule ATP, showing that energy production in the organelles is not crucial to these effects, Okwan-Dodo says.