Brain tumors are never good news, but when they come in a specific variety, the tumor cells can reprogram immune cells as they invade, effectively paralyzing the body's immune defense against the tumor. But a team of scientists is working to nullify this tactic.
Researchers have discovered the mechanism brain tumors use to "paralyze" the immune system and simultaneously learned how to reactivate it to target the brain tumor, according to a new study published in the journal Nature.
And as a bonus: this study confirms that therapeutic vaccines (also called immunotherapies) have a greater effect on brain tumors if active substances are simultaneously used to revitalize the immune system.
How cancer-containing gliomas 'paralyze' the immune system
Diffuse gliomas are typically an incurable type of brain tumor that rapidly spreads in the brain. Sadly, they're also quite hard to remove completely via surgery. Radiotherapy and chemotherapy alas can only do so much, which leaves oncologists in urgent need of unconventional treatments and approaches to combat gliomas -- in this case, using the immune system, via immunotherapies or therapeutic vaccines. But there's more to gliomas than cancer cells alone. Up to 50% of its mass consists of microglia cells, phagocytes of the brain itself, in addition to macrophages moving into the tumor via blood vessels. Macrophages are also scavengers, but they aren't great at combatting tumor cells.
"If we are to make progress in developing immunotherapies or therapeutic vaccines, we need to understand exactly how the immune environment behaves during tumor development," said Director of the Department of Neurology Michael Platten, of the University Medicine Mannheim, who is also Head of Division at the German Cancer Research Center (DKFZ), in addition to directing the present study. "Moreover, we were interested in whether special genetic features of the gliomas have a particular influence on the function of the glioma-associated immune cells." Platten's colleagues joined forces with Medical Director Marco Prinz of the Institute of Neuropathology in Freiburg, along with his own working group.
Together, they published a "status analysis" of the immune cells associated with glioma, in another study, just published in Nature Cancer. In studying the protein profiles and RNA of different microglia cells and macrophages and employing tumor models in mice, the team of researchers was also able to analyze the immune-system environment throughout the "lifespan" of the disease. Of special interest to the researchers was the "IDH mutation" of tumors, which is present in roughly 70% of all low-grade gliomas. These tumor cells possess the same mutation linked to a specific protein building block that's exchanged within the IDH* enzyme, according to an embargoed release shared with IE.
A mutation in gliomas enables them to protect themselves against the immune system
Because of the IDH mutation, glioma cells release a metabolic product called (R)-2-HG, which promotes cancer, and manipulates invading macrophages. In short, the scavenger cells are reprogrammed, which blocks the immune system retaliation against the tumor. "Ultimately, the IDH mutation enables the gliomas to protect themselves against the human immune system," said DKFZ Researcher Mirco Friedrich, who is also a physician at Heidelberg University Hospital, in addition to a lead author on the study.
Brain tumors are obviously serious, not least of which because of how difficult it is to surgically remove them from the most important organ in the human being. With a "paralyzed" immune system, medical professionals have few options to treat tumors in the brain, which is why they're so often fatal. But with this new research, we may one day be able to empower the body's immune system by reactivating it. And this could make the difference between life or death in victims of cancer.