Scientists in Canada report a discovery that could lead to better treatment for patients suffering from brain cancer. The researchers looked at human glioblastoma samples and found that specialized immune cells in brain tumor patients are compromised. The team took this discovery and, in an animal model, identified a drug that is able to reactivate those immune cells and reduce brain tumor growth, thereby increasing the lifespan of mice two to three times.
The University of Calgary Hotchkiss Brain Institute’s (HBI) V. Wee Yong, Ph.D., and research associate Susobhan Sarkar, Ph.D., and their team, including scientists from the department of clinical neurosciences and the university’s Southern Alberta Cancer Research Institute published their findings in Nature Neuroscience. The title of their paper was “Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells.”
“We examined whether the microglia and macrophages that are abundant in gliomas alter BTIC [brain tumor initiating cells] growth. We found that microglia derived from nonglioma human subjects markedly mitigated the sphere-forming capacity of glioma patient-derived BTICs in culture by inducing the expression of genes that control cell cycle arrest and differentiation,” wrote the investigators. “This sphere-reducing effect was mimicked by macrophages, but not by neurons or astrocytes. Using a drug screen, we validated amphotericin B (AmpB) as an activator of monocytoid cells and found that AmpB enhanced the microglial reduction of BTIC spheres.”
“Microglia are the brain’s own dedicated immune system,” explains Dr. Yong. “And in this study, we have formally demonstrated for the first time that these cells are compromised in living brain tumor patients.”
“This drug [AmpB] was able to reactivate the disabled microglia,” says Dr. Sarkar, “thus restoring the body’s natural defense mechanisms and restricting the growth of brain tumor initiating cells.”
The drug they identified is a powerful agent that is already used clinically to treat severe fungal infections of the brain and spinal cord. Drs. Yong and Sarkar hope this discovery will lead to clinical trials and ultimately to a new standard of care for brain tumor patients.