Drug treatment could suppress cancer cells in the brain
The growth of brain tumor initiating cells (BTICs) positively linked to glioma development and recurrence may be altered by drug immunotherapy, according to a study published online Dec. 8 by Nature Neuroscience.
Susobhan Sarkar, PhD, a research scientist from the department of clinical neurosciences at the University of Calgary in Alberta, Canada, and colleagues discovered that numerous microglia and macrophages changed how BTIC grow in gliomas. Further investigation showed that non-glioma microglia from human subjects diminished the capacity of BTIC to form properly.
“We found that microglia derived from non-glioma 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 authors.
The mitigating effect of microglia was repeated by macrophages, but it was limited to the two and could not be recreated in tests with astrocytes or neurons. The researchers then utilized a drug screen and tested amphotericin B (AmpB) to see if it would initiate monocytoid cells. Results of the drug test showed that AmpB was able to reduce the ability of BTIC to form into typical spheres. Daily systemic immunotherapy with nontoxic doses of AmpB significantly improved survival in animal studies of mice with intracranial mouse or human BTIC.
“Notably, microglia and monocytes cultured from glioma patients were inefficient at reducing the sphere-forming capacity of autologous BTICs, but this was rectified by AmpB,” wrote the researchers.