Scientists from Brigham and Women's Hospital and MIT employed nanotechnology to identify a novel method that cancer may neutralize its would-be cellular adversaries. Immune cells are depleted, and cancer cells are boosted by slurping out the immune cell's mitochondria.
Research published in Nature Nanotechnology suggests that the next generation of cancer immunotherapy may have a different target.
Shiladitya Sengupta, the corresponding author of the study and co-director of the Brigham's Center for Engineered Therapeutics, stated, "Cancer kills when the immune system is inhibited, and cancer cells are allowed to spread, and it looks that nanotube may help them accomplish both." When it comes to cancer cells evading the immune system, "this is an entirely new process, and it provides us with a new target to pursue."
Sengupta and colleagues co-cultured breast cancer cells with immune cells such as T cells to study the nanoscale interactions between cancer cells and immune cells.
They noticed something strange when they used field-emission scanning electron microscopy: Immune cells and cancer cells seemed to be physically linked by thin tendrils, with diameters ranging from 100 to 1000 nanometers.
Some of the nanotubes formed thicker tubes as they came together. As a result, they used a fluorescent dye to label mitochondria from T cells. They observed that the mitochondria were sucked out of the immune cells and delivered to cancer cells through the nanotube system.
According to co-corresponding author Hae Lin Jang, Ph.D., a principal investigator at the Center for Engineered Therapeutics, "by carefully preserving the cell culture condition and observing intracellular structures, we saw these delicate nanotubes, and they were stealing the energy source of the immune cells." In cancer cells, this type of activity has never been seen previously. When working with nanotubes, which are pretty delicate, we had to be extremely careful with the cells to avoid damaging them.
The scientists next investigated what would happen if they blocked the cancer cells from gaining access to mitochondria. Using mice models of lung and breast cancer, scientists found that tumor development was significantly reduced when an inhibitor of nanotube production was administered.
"Finding combinations of medicines that potentially enhance outcomes is one of the aims of cancer immunotherapy," said lead author Tanmoy Saha, Ph.D., a postdoctoral researcher at the Center for Engineered Therapeutics. "Based on our findings, it seems that a nanotube formation inhibitor might be paired with cancer immunotherapies and examined to determine whether it improves patient outcomes."
Saha, T., Dash, C., Jayabalan, R. et al. Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells. Nat. Nanotechnol. (2021). https://doi.org/10.1038/s41565-021-01000-4