A ULB study reveals a new advance in our understanding of the immune system of the naked mole rat, opening up prospects for cellular immunotherapy of cancer.
During the development of cancer, the immune system is able to exert antitumor activity thanks to natural killer (NK) cells and T lymphocytes. While it is naturally rare for the immune system to react effectively to the proliferation of cancer cells, the induction of a more significant and specific immune response has become an essential therapeutic focus in the fight against cancer.
The naked mole rat is a small rodent from East Africa with a very particular lifestyle, almost exclusively underground. For example, it has a sensory system that is extremely sensitive to ground vibrations and, strangely enough, develops very few cancers (6 cases out of thousands of animals monitored), even though, unlike humans, it lacks canonical NK cells, which are capable of killing tumor cells.
Faced with this duality, Prof. David Vermijlen, researcher at the WEL Research Institute, laboratory director and professor at the Faculty of Pharmacy , and Guillem Sanchez Sanchez , investigated the specifics of the naked mole rat’s immune system, in collaboration with the laboratory of Vera Gorbunova (University of Rochester, NY, USA), a specialist in this fascinating animal. The results of their study have just been published in the journal Nature Communications.
While certain biochemical properties, such as the high cellular production of hyaluronic acid, have been suggested to explain the naked mole rat’s resistance to tumor development, it has been proposed more recently that the animal’s immune system may also play an essential role. Like humans, the naked mole rat has a thoracic thymus: an organ located in the upper thorax, around the esophagus and between the lungs. It is the site of the formation of T lymphocytes, a major immune cell population. However, in contrast to humans, the naked mole rat has a second thymus, in the cervical region. What’s more, neither thymus shrinks with age, unlike human thymuses. Finally, these thymuses are biased towards the generation of unconventional immune cells, gammadelta T lymphocytes. This was enough to intrigue Prof. Vermijlen, a specialist in this type of T lymphocyte:
"Gammadelta T cells have a high anti-cancer potential. We therefore wondered whether, in the naked mole rat, these cells could help prevent the formation of tumors".
" This project is the fruit of a cooperative effort between scientists from various disciplines: immunology, genomics and naked rat biology. "explains Guillem Sanchez Sanchez, first author of the study and PhD student in Prof. Vermijlen’s laboratory. The study identified a specific subpopulation of naked mole rat gammadelta T cells, called V g 4-2/V d 1-4, which are preprogrammed to exert antitumor activity similar to human NK cells. Above all, these cells express chains that recognize a specific ligand, which could help distinguish tumor cells from healthy cells.
The study by Guillem Sanchez Sanchez and Prof. Vermijlen suggests that the continuous production of V g 4-2/V d 1-4 gammadelta T cells in the thymus could actively control cancer cell formation throughout the life of the naked mole rat.
A new therapeutic perspective for cellular immunotherapy of cancer " This discovery opens up a new therapeutic perspective to be explored in the context of cellular immunotherapy of cancer " comments David Vermijlen. " The potential recognition of cancer cells by the naked mole rat’s gammadelta T-cell receptor could be studied in an animal model to determine whether cell therapy using this T-cell receptor would be effective ".
The anti-cancer biology of the naked mole rat is still intriguing.