Brain cancer treatment may lie in reactivating immune cells

Brain cancer treatment may lie in reactivating immune cells


When they examined tumor samples of glioblastoma, the deadliest form of brain cancer,

researchers in Canada discovered they contained deactivated forms of specialized immune cells that

normally fight tumor-generating cells. When they tested a drug that reactivates these immune cells

in diseased mice, the animals lived two to three times longer.

The researchers, from the University of Calgary’s Hotchkiss Brain Institute (HBI) and Southern

Alberta Cancer Research Institute, hope their discovery will lead to clinical trials and eventually

to a new standard of care for brain tumor patients.

They write about their findings in a recent online issue of Nature Neuroscience.

Even though treatments already exist, the median survival for patients with glioblastoma is only 15 months – fewer than 1 in 20 survive more than 5


Microglia ‘battle for the brain’ against cancer cells

Our brains have their own specialized immune cells called microglia that protect against injury

and infection.

They are the brain’s “dedicated immune system,” explains senior author V. Wee Yong, a professor

in Calgary’s Departments of Oncology and Clinical Neurosciences.

As with other cancers, brain tumors start from stem cells. In the case of brain tumors, they are

called brain tumor initiating cells (BTICs).

BTICs grow and divide rapidly, eventually forming a mass, the tumor itself.

And, as with cancers in other parts of the body, immune cells – like microglia – detect these kinds

of cells and try to eliminate them.

Prof. Yong, who also holds a Canada Research Chair in Neuroimmunology, says:

“We refer to this as the battle for the brain, in which early on in the disease, the microglia

are trying to destroy the brain tumor initiating cells. But over the course of time, the tumor

disables the microglia and we start to see more initiating cells and more rapid tumor growth.”

He explains that what they sought to do in their study was find a way “to tip the battle in

favor of the brain to suppress the tumor.”

Reactivating microglia led to tumor reduction

In the first part of the study, he and his colleagues took microglia from patients without

gliomas and cultured them with BTICs from patients with gliomas. They found that the microglia were

able to arrest the growth of BTICs by inducing the expression of some of their genes.

Then in a second part of the study, in mice with brain tumors caused by mouse and human-derived

BTICs, they found that daily doses of the drug amphotericin B (AmpB) reactivated microglia and led

to a significant reduction in tumor growth.

First author and research associate Dr. Susobhan Sarkar says:

“This drug was able to reactivate the disabled microglia, thus restoring the body’s natural

defense mechanisms and restricting the growth of brain tumor initiating cells.”

AmpB is a powerful drug that is already used to treat severe fungal infections of the brain and

spinal cord.

“It’s a rather harsh medication,” says Prof. Yong. “But we have demonstrated that this drug can be used in very

small doses where it is not only well tolerated, but it is also effective in re-programming


The team’s discovery is already drawing attention from researchers in other parts of Canada. One

of these is the internationally renowned neurosurgeon and brain tumor expert James Rutka, professor

and chair of the Department of Surgery at the University of Toronto, who comments:

“This research is highly significant as it implies that a commercially available drug,

amphotericin B, which has never been used before for patients with gliomas, may be a novel

treatment to consider in future trials of patients with this frequently lethal cancer.”

Funding from the study came from Alberta Innovates – Health Solutions/Alberta Cancer


Earlier this year, a team from Johns Hopkins University School of Medicine in the US

reported how they found a patient’s

own fat may help fight glioblastoma. They discovered a form of stem cell, called mesenchymal

stem cells (MSCs), can hunt down cancer cells and that these stem cells are present in patients’

own fat.

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1 thought on “Brain cancer treatment may lie in reactivating immune cells”

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