The blood-brain barrier is a type of fortress that consists of barriers to keep dangerous pathogens away. However, protection comes at a cost: these barriersaffect the immune system, as they face serious threats such as glioblastoma, a deadly brain tumor for which there are few effective treatments. Yale researchers have now found a novel way to bypass the brain's natural defenses when they are counterproductive.
Break through the blood brain barrier
By pushing the saviors of the immune system through the drainage system of the fortresses, the scientists achieved this breakthrough. “People had believed that the immune system could do very little against brain tumors,” said senior corresponding author Akiko Iwasaki. “There was no opportunity for glioblastoma patients to benefit from immunotherapy.”
While the brain itself has no direct way to dispose of cellular debris, tiny vessels that line the interior of the skull collect remaining tissue and dispose of it through the body's lymphatic system, which filters toxins and waste from the body. Accordingly, the researchers used this disposal system in the new study. These vessels form shortly after birth, driven in part by the gene known as vascular endothelial growth factor C, or VEGF-C.
The team introduced VEGF C into the cerebrospinal fluid of mice with glioblastoma and observed an increased T cell response to tumors in the brain. When combined with immune system checkpoint inhibitors commonly used in immunotherapy, VEGF-C treatment significantly extended the survival of the mice. In other words, the introduction of VEGF-C in conjunction with cancer immunotherapeutics was apparently sufficient to combat brain tumors.
Research results
“These results are remarkable,” Iwasaki said. “We would also like to use this treatment in glioblastoma patients. The prognosis for current surgical and chemotherapy therapies is still as bleak.”
Other authorsfrom Yale are Tianyang Mao, Huiping Dong, Ligia Simoes, Braga Boisserand and Marcus Bosenberg. Salli Antila and Kari Alitalo from the University of Helsinki are also authors. This study was funded primarily by the Howard Hughes Medical Institute and the National Institutes of Health.
