Research press release


Nature Neuroscience

Blunting brain tumor growth with immune activation



V. Wee Yongたちは、患者の脳腫瘍に由来する免疫細胞について、BTICの成長に対する影響を調べた。Yongたちは、患者由来の免疫細胞がBTICの拡大を和らげるのにあまり効果がないことを発見した。ところが、脳腫瘍ではない患者から得た小膠細胞やマクロファージはBTICの成長を減少させた。そこでYongたちは低分子化合物のライブラリを調べ、アムホテリシンB(AmpB)という薬物を同定した。これは、マクロファージと小膠細胞を活性化して作用し、BTIC増殖を減らす。AmpBをヒト患者由来のBTICを持つマウスに投与したところ、生存期間がほぼ2倍になり、脳腫瘍の成長が目覚ましく減少した。


Pharmacologically stimulating immune cells in the brain can reduce the proliferation of cancer-forming stem cells in a mouse model of brain cancer, reports a study published online this week in Nature Neuroscience. This study also identifies a potential therapeutic drug to combat one of the most aggressive forms of brain tumor, called glioblastoma.

Malignant brain tumors are often resistant to conventional therapies because of the presence of tumor-forming stem cells called brain tumor initiating cells (BTICs). BTICs are stem-like cells that can self-renew. In patients with gliobastomas, BTICs are often surrounded by immune cells, such as microglia and macrophages that that constantly survey the central nervous system tissue and provide the first line of immune defense.

V. Wee Yong and colleagues examined the immune cells derived from brain tumors in patients for their effects on BTIC growth. They found that patient-derived immune cells perform poorly in mitigating BTIC expansion. However, microglia and macrophages from non-brain tumor patients reduced the growth of BTICs. Yong and colleagues then tested a library of small molecule compounds and identified a drug called amphotericin B (AmpB), that works by activating macrophages and microglia to lessen BTIC proliferation. When AmpB was administered to mice with human patient-derived BTICs, there was a nearly doubled survival age and significantly reduced brain tumor growth.

Although AmpB is an anti-fungal medication already approved by the US Food and Drug Administration, the drug is known to have severe - and potentially lethal - side effects of fever induction and multiple organ failure when used in high intravenous doses. Further studies are needed to determine the safety and feasibility of using AmpB and similar immune-activating drugs as potential gliobastoma treatments.

doi: 10.1038/nn.3597

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