The brain is a sort of fortress, equipped with barriers designed to keep
out dangerous pathogens. But protection comes at a cost: These barriers
interfere with the immune system when faced with dire threats such
glioblastoma, a deadly brain tumor for which there are few effective
treatments.
Yale researchers have found a novel way to circumvent the brain’s
natural defenses when they’re counterproductive by slipping immune system rescuers
through the fortresses’ drainage system, they report Jan. 15 in the journal Nature.
“People had
thought there was very little the immune system could do to combat brain
tumors,” said senior corresponding author Akiko Iwasaki. “There has been no way
for glioblastoma patients to benefit from immunotherapy.”
Iwasaki is the
Waldemar Von Zedtwitz Professor of Immunobiology and professor of molecular,
cellular, and developmental biology and an investigator for the Howard Hughes
Medical Institute.
While the brain
itself has no direct way for disposing of cellular waste, tiny vessels lining
the interior of the skull collect tissue waste and dispose of it through the
body’s lymphatic system, which filters toxins and waste from the body. It is
this disposal system that researchers exploited in the new study.
These vessels
form shortly after birth, spurred in part by the gene known as vascular
endothelial growth factor C, or VEGF-C.
Yale’s Jean-Leon
Thomas, associate professor of neurology at Yale and senior co-corresponding
author of the paper, wondered whether VEGF-C might increase immune response if
lymphatic drainage was increased. And lead author Eric Song, a student working
in Iwasaki’s lab, wanted to see if VEGF-C could specifically be used to
increase the immune system’s surveillance of glioblastoma tumors. Together, the
team investigated whether introducing VEGF-C through this drainage system would
specifically target brain tumors.
The team
introduced VEGF C into the cerebrospinal fluid of mice with glioblastoma and
observed an increased level of T cell response to tumors in the brain. When
combined with immune system checkpoint inhibitors commonly used in
immunotherapy, the VEGF-C treatment significantly extended survival of the
mice. In other words, the introduction of VEGF-C, in conjunction with cancer
immunotherapy drugs, was apparently sufficient to target brain tumors.
“These results
are remarkable,” Iwasaki said. “We would like to bring this treatment to
glioblastoma patients. The prognosis with current therapies of surgery and
chemotherapy is still so bleak.”
Journal article: https://www.nature.com/articles/s41586-019-1912-x
No comments:
Post a Comment