Longevity Briefs: Cancer Sabotages The Immune System By ‘Gifting’ Mitochondria

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

The immune system is able to recognise and eliminate cancer cells, which means that in order to spread, a tumour needs to develop mutations that allow it to evade destruction by the immune system in some way. In this study, researchers reveal a new and fascinating way in which cancer cells achieve this, and a potential target for future cancer treatments.

The discovery:

The researchers began by analysing clinical specimens from various human cancers. Specifically, they studied mutations in the mitochondrial DNA (mtDNA) of both the cancer cells and the lymphocytes (a type of white blood cell) that are within the tumour attempting to destroy it. Mitochondria, the power plants of the cell, were once separate organisms in their deep evolutionary past and still retain parts of their DNA that encode essential mitochondrial proteins.

The researchers found that the mitochondria in the cancer cells and the lymphocytes shared many of the same deleterious mutations, suggesting that mitochondria might have been transferred between them. To investigate this, they tracked mitochondrial transfer in culture using a fluorescent protein, and found that mitochondria were indeed transferred from cancer cells to T cells (a type of lymphocyte). Not only were these faulty mitochondria transferred over to the lymphocytes, but they were also resistant to mitophagy – the process by which cells eliminate mitochondria that are defective. This was found to be due to the transfer of mitophagy-inhibiting molecules alongside the mitochondria.

Finally, the researchers studied this process in mice, and found that T cells bearing mitochondria originating from cancer cells were significantly worse at killing cancer cells. However, when the researchers gave mice a molecule to inhibit the release of small extracellular vesicles, one of the main pathways for mitochondrial transfer, they found that tumour growth was slowed and the mice became more responsive to immunotherapy. 

The implications:

So, it seems as though cancer cells are capable of ‘sabotaging’ the immune cells that are attempting to destroy them by giving them defective mitochondria, alongside molecules that block mitophagy. Mutations in mitochondrial DNA are common because mtDNA is exposed to a lot of chemical damage compared to the DNA within the cell’s nucleus. These mutations occur in all cells as we age, causing the mitochondria to become less efficient with severe consequences for the ability of the cell to function. In a way, cancer is evading immune detection by accelerating ageing of the immune cells that are trying to kill it.