Shiladitya Sengupta is co-director of the Brigham’s Center: “Cancer kills when the immune system is suppressed and cancer cells can progress to metastasis, and nanotubes are involved in both processes.” In order to grow, enlarge and spread, cancer cells need to go unnoticed by the immune system. Almost pass one of them. A team of researchers from Brigham and Women’s Hospital and MIT released an extraordinary finding on November 18 in the journal Nature Nanotechnology. Cancer stretches out elongated nanoscale tentacles to reach immune cells and literally extract energy from the immune cell. It does this by stealing the mitochondria from the hacked cells. With this extracted energy, the cancer cell is activated in exchange for deactivating the immune cell. A real hack, something like a mitochondrial phishing.
Sengupta and the rest of the team grew breast cancer cells together with immune cells, such as T cells. To investigate the metabolism of cancer cells and the interaction with their neighboring cells, field emission scanning electron microscopy was used ( FESEM). It was when they found the existence of a real physical connection between the two types of cells. They are small tentacles with tiny diameters: between 100 and 1000 nanometers. Taking into account that human hair has a diameter of approximately 80,000 nanometers, we could put a bunch of 80 to 800 tentacles of this type in one of our hairs. It is understandable that they went almost unnoticed, given the dimensions. The researchers also commented that the manipulation of the cells has been complex, since these nanotubes are fragile and break easily. But they saw not only the nanotubes, but also what was running inside them. The team stained the mitochondria of T cells green and were able to see how they were absorbed by cancer cells through these tiny tentacles. As Sengupta has stated, “this is a completely new mechanism by which cancer cells evade the immune system and gives us a new point of view for further investigation.”
Mitochondria are the cellular organelles responsible for supplying the greatest energy supply so that the cell can carry out its metabolic activities. A cell without energy dies. So the next step taken by the working group was to cut the supply of mitochondria, that is, “cut off the light.” They wondered what would happen if they prevented the malicious cells from being able to hijack the mitocons for themselves. And they did. With an inhibitor that prevented the formation of nanotubes and that was already known from experimentation with mice to study lung and breast cancer. They were able to observe that, indeed, tumor growth was significantly reduced. “It was very exciting, because this type of behavior has never been seen in cancer cells before,” said Hae Lin Jang, one of the authors.
Combination therapy is one of the best bets for the fight against cancer. The research team itself has noted that the combination of the use of inhibitors for the formation of nanotubes together with immunotherapy could improve the results in patients. Quite a challenge full of hope.
Several previous studies showed an interconnection by nanotubes between different types of cells. The interaction and transfer of mintochondria between healthy and apoptotic cells (cells with a death programmed by the organism itself) had even been studied. In this context we speak of “tunnelled nanotubes” (TNT’s). In the study Tunneling nanotubes promote intercellular mitochondria transfer followed by increased invasiveness in bladder cancer cells (Oncotarget, 2017) TNT’s could be observed between bladder cancer cells, and mitochondria transfer between them, as if they were making an energetic bizum between good friends . Therefore, mitochondrial exchange is a process in which attention has been paid for a long time and a door towards a possible quite effective therapy. And, on the other hand, it was also known that mitochondria are necessary for active T cells, as can be seen in the paper Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling (Immunity, 2013). Finally, staining techniques have been optimized in recent years to levels that appear to be on the plane of science fiction. It is a delight for the eyes to take a look online at the search results “MitoTracker ®”. These are fluorescent dyes that allow the semi-quantitative measurement of the mitochondrial content of a cell using flow cytometry. Therefore, the novelty of this study is to see how mitochondria are stolen from T cells by breast cancer cells.
The Brigham and Women’s Hospital has issued a press release with a preview of the article published in Nature Nanotechnology that has served as the basis for this adaptation. This original article has the title Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells .
