In the US, researchers found that cancer cells siphoning mitochondria from immune cells with pipette-like nanotubes and draining their energy. Blocking nanotube formation could make certain cancer treatments more effective.
Cancer cells have to escape the immune system to grow and spread. One way to do this is to place proteins on the surfaces of immune cells that reduce their ability to kill themselves. A type of cancer treatment called immune checkpoint suppression blocks these proteins from interacting with immune cells. The treatment allows the immune cells to kill the cancer more efficiently. But this treatment doesn’t work in all cases, suggesting that cancer cells have other ways to evade the immune system.
A team of researchers led by Doctors Hae Lin Jang and Doctor Shiladitya Sengupta, from Brigham and Women’s Hospital at Harvard Medical School in Boston, discovered how cancer cells get rid of the immune system by growing human and mouse breast cancer cells with T cells, a type of immune cell. researched.
Using electron microscopy, the researchers saw long, hollow extensions called nanotubes that connect cancer cells and T cells. Similar structures used to transfer materials between cells have been found in previous research.
They then stained the mitochondria within the T cells, which produce energy for the cells, with a fluorescent dye. Sixteen hours after adding these stained cells to a cancer cell culture, they found that fluorescent mitochondria from the immune cells were moving along the nanotubes towards the cancer cells. This transfer was largely one-way. Mitochondria did not go from cancer cells to T cells.
Mitochondria transfer affected the metabolism of both cell types. Cancer cells consumed oxygen faster when they grew together with T cells. This showed that the mitochondria in cancer cells produced more energy. Cancer cells also grew larger in the presence of T cells. Meanwhile, the amount of T cells decreased rapidly.
The team tried to circumvent the mechanism cells use to create the nanotubes in several ways. In each trial, mitochondrial transfer to cancer cells was decreased. This means that targeting nanotube formation can be used for therapeutic purposes.
The researchers tested this idea on mouse guinea pigs with breast cancer. They treated the mice with a combination of a nanotube formation suppressor and an immune checkpoint suppressor. The combination reduced tumor growth more than either drug used alone.
The results show that cancer cells are siphoning mitochondria from T cells. This causes the cancer cells to energize and also disables the immune cells. Inhibiting nanotube formation could thereby increase the effectiveness of immune checkpoint suppressive therapies for cancer.
The researchers note that the nanotube suppressors they tested have other effects. Compounds that specifically target nanotube formation will need to be developed before the treatment can be tested in patients.
“Cancer is lethal when the immune system is suppressed and cancer cells can metastasize,” said Doctor Sengupta, who led the research team, and noted that nanotubes can cause both problems. Sengupta said that nanotubes are a new mechanism that allows cancer cells to escape from the immune system. “It gives us a new target to pursue,” he said.
The research, supported by the National Institutes of Health of the US Department of Health, was published in the monthly peer-reviewed scientific journal Nature Nanotechnology.