Researchers have discovered how a glitch in the brain’s immune system can inadvertently cause an accelerated growth and spread of brain tumors. However, therapeutically “fixing” this failure to restore the activity of the immune system can halt the progression of these deadly, aggressive cancers.
“Glioblastoma is the deadliest type of cancer in the central nervous system, accounting for most malignant brain tumors,” explained Professor Ronit Satchi-Fainaro from Tel Aviv University, lead author of the study. “It is aggressive, invasive, and fast-growing, making it resistant to existing treatments, with patients dying within a year of the cancer’s onset.”
“Moreover, glioblastoma is defined as a ‘cold tumor’, which means that it does not respond to immunotherapeutic attempts to activate the immune system against it.”
Neural tissue is guarded by a specialized immune cell unique to the brain called microglia. However, until now, neuroscientists were not clear as to why microglia fail to detect and eliminate glioblastomas. Satchi-Fainaro and colleagues took a closer look at brain tissue samples from glioblastoma patients and made a surprising discovery.
“To our surprise, we found that not only do the microglia cells do nothing to stop the cancer cells, they actually play a crucial and negative role by accelerating the division, spread, and mobilization of glioblastoma cells,” said Satchi-Fainaro.
The team identified the mechanism behind this curious phenomenon: a protein called P-Selectin, or SELP. Under normal conditions, SELP facilitates the movement of cells, such as the passage of white blood cells as they travel within blood vessels. The researchers found that glioblastoma cells caused microglia to churn out abnormally large quantities of SELP, which gave the cancer cells the power to infiltrate brain tissue faster.
Fascinatingly, the scientists found that silencing SELP synthesis in microglia slowed down tumor growth and halted the migration of glioblastoma cells, pumping the brakes on cancer progression.
Whether or not SELP inhibitors will work in glioblastoma patients will be the subject of future clinical trials. “Our treatment may be the needed breakthrough in the battle against the most daunting cancer of all,” commented Satchi-Fainaro.
Sources: Nature Communications, Tel Aviv University.