Cancers must evade the immune system to progress. Gaining a better understanding of how cancer cells do this is critical in the search for the development of next-generation immunotherapies. Cells can form connections via nanotubes – tiny structures made up of the protein actin – to transport materials between them. By using these structures to hijack immune cells' mitochondria cancer cells can gain power to grow and divide more quickly, while depleting the immune cells' ability to function.
'Cancer kills when the immune system is suppressed and cancer cells are able to metastasise, and it appears that nanotubes can help them do both,' said corresponding author Dr Shiladitya Sengupta from the Brigham and Women's Hospital in Boston, Massachusetts. This is a completely new mechanism by which cancer cells evade the immune system and it gives us a new target to go after.'
Researchers from the Centre for Brigham and Women's Hospital and MIT in Massachusetts grew mouse immune and cancer cells together in a dish for 16 hours and used field-emission scanning electron microscopy to take a snapshot of the interactions that formed. The results, published in Nature Nanotechnology, showed that, on average, each cancer cell formed one nanotube connection with an immune cell called a T-cell. The connected cancer cells consumed double the amount of oxygen and divided more often than cancer cells that had been grown close to, but physically apart from T-cells. The oxygen consumption of the T-cells and their numbers decreased significantly when they were in contact with the cancer cells.
The same results were found in human thymus and breast cancer cells. The researchers used fluorophore-tagged mitochondria and discovered that they were transported along the nanotubes from the T-cells to the cancer cells.
The researchers used a drug that partially inhibited the formation of nanotubes, together with the clinically available checkpoint inhibitor PD-1 in mice, and found that it reduced the tumour size and increased the number of T-cells present in the tumours.
Lead author Dr Tanmoy Saha from the Centre for Engineered Therapeutics at the Brigham and Women's Hospital said 'One of the goals in cancer immunotherapy is to find combinations of therapies that can improve outcomes. Based on our observations, there is evidence that an inhibitor of nanotube formation could be combined with cancer immunotherapies and tested to see if it can improve outcomes for patients.'