Recently, scientists have discovered that nanotubules transfer mitochondria from immune cells to cancer cells to metabolically empower the cancer cells. This is thought to help cancer cells evade the immune system.
To survive and spread, cancer cells must evade the immune system. The current understanding of tumour immune evasion is primarily based on the capacity of cancer cells to express ligands that engage with immune checkpoints. Blocking these checkpoints can lead to clinical benefits, but only a small proportion of cancer patients currently respond to such immunotherapies. Hence, investigating these alternative immune evasion strategies, and subsequently inhibiting them, could be critical towards developing more effective antitumour treatments.
Cancer nanotubules and mitochondria
Recently, investigators from Brigham and Women’s Hospital and Massachusetts Institute of Technology tested for nanotube-mediated transfer of mitochondria between cancer cells and immune cells. They co-cultured different murine and human breast cancer cells with effector immune cells, such as natural killer T or CD3+/CD8+ T cells and examined the intercellular interactions using field-emission scanning electron microscopy. The results were published in Nature Nanotechnology and are hoped to lead to new targets for immunotherapies against cancer.
Mitochondrial function is essential to a number of processes, including cytokine production and effective memory response. Additionally, mitochondrial gain and increased oxidative phosphorylation has been implicated in cancer progression and resistance to chemotherapy. In this study, interestingly, the microscopy image analysis revealed that cancer cells and immune cells connected through nanoscale tube-like structures, mostly around 10-30 µm in length and 100-1,000 nm in width. It was found that a single nanotube arising from a cancer cell could connect with several immune cells, and in some cases, the nanotubes aggregated to form a thicker nanotube.
The team then tested for nanotube-mediated transfer of mitochondria between cancer cells and immune cells by labelling the mitochondria within the natural killer T cells. It was found that after just 16 hours, there was substantial levels of mitochondrial transfer from the immune cell to the cancer cells. Additionally, inhibiting the nanotube assembly machinery resulted in a significant reduction in the mitochondrial transfer and prevented the depletion of immune cells.
Shiladitya Sengupta, Co-Director of the Brigham’s Center for Engineered Therapeutics, said:
“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. This is a completely new mechanism by which cancer cells evade the immune system and it gives us a new target to go after.”
Nanotube-mediated mitochondrial hijacking
Essentially, the researchers in this study discovered that cancer cells can hijack the mitochondria from immune cells via nanotubules. Moreover, they found that the nanotubule transfer of mitochondria from immune cells to cancer cells metabolically empowers the cancer cells and leaves the immune cells depleted. These findings suggest that nanotubule-mediated mitochondrial hijacking from immune cells could emerge as a novel mechanism of immune evasion by cancer cells and could also contribute to the development of more effective immunotherapy agents for cancer.
Tanmoy Saha, a postdoctoral researcher in the Center for Engineered Therapeutics, explained:
“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.”
Image credit: Medical News Today