When cancer that starts within the body metastasizes to the brain, it is sort of at all times lethal, partly because so few treatment options exist. Now a latest study by Wistar scientists published in Nature Communications shows that a kind of brain cell called astrocytes plays a vital role in promoting brain metastasis by recruiting a selected subpopulation of immune cells.

Image Credit: Wistar Institute

The finding could possibly be a primary step toward identifying potential targets for therapies to fight cancers that metastasize to the brain. This could fill a big unmet need, said researcher Qing Chen, M.D., Ph.D., assistant professor, Immunology, Microenvironment & Metastasis Program, Ellen and Ronald Caplan Cancer Center, because treatment options for brain metastasis have lagged behind, at the same time as advances in other cancer therapies have made enormous strides, making those cancers rather more treatable.

“It could be devastating for patients and their families, because they undergo a lot treatment, they survive the breast cancer, all of them rejoice, after which it shows up within the brain,” resulting in a terminal diagnosis, she said. 

Several varieties of cancer are known for metastasizing to the brain, including breast, lung, carcinoma, and melanoma. One reason conventional treatments don’t work on these cancers after they reach the brain is since the brain is such a distinct environment from the remaining of the body, with unique brain cells (neuron and glia cells) providing different support to the metastatic cancer cells.

For the study, researchers wanted to raised understand the cancer-brain interactions that trigger metastasis when cancer cells enter the brain. They focused on astrocytes, a kind of star-shaped cell that helps form connections between neurons.

Using brain metastasis mouse models, researchers showed that when the astrocytes were exposed to cancer cells, they began to activate type I interferon pathways. Type I interferon, the cytokines related to regulating inflammation, have been shown to need to anti-tumor effects. Nonetheless, increasingly more evidence suggest controversial effects of type I IFN signaling in chronic inflammation and cancer.

“That was an exciting surprise,” Chen said, adding that it was the primary time the sort I interferon response had been implicated to advertise brain metastasis.

They found that the interferon response was being activated at a low level but for a chronic time frame. This might explain why a process that is generally related to helping the immune system was actually causing harm by supporting tumor growth. Previous studies have found that low-level, chronic interferon response could cause negative health outcomes, she noted.

After they took a more in-depth look, researchers found that the interferon signaling was activating production of a chemokine called CCL2, which in turn attracted harmful immune cells called monocytic myeloid cells. These cells promote tumor growth.

Researchers then studied mice that were genetically altered to abolish the sort I interferon activation in astrocyte cells. They found that mice that were missing this pathway had fewer brain metastases.

“That shows the sort I interferon response in astrocyte cells actually promotes metastasis,” Chen said.

She noted researchers found an identical result with each melanoma and breast cancer cells, showing that the method – and potential therapeutic targets – occur across different cancer types.

Chen hoped the findings encouraged more researchers to check the interactions that lead cancers to metastasize within the brain.

It’s an urgent must have more people concentrate to this problem, and hopefully we’ll have more basic researchers and clinicians take part in future studies, in addition to more resources.”

Qing Chen, M.D., Ph.D., Assistant Professor, Immunology, Microenvironment & Metastasis Program, Ellen and Ronald Caplan Cancer Center

Next, Chen’s team is applying for a federal grant from the National Cancer Institute (NCI) for a follow up study to raised understand the mechanism and timing of how astrocytes and the interferon response promote brain metastasis, with a goal of identifying one of the best therapeutic window for treating and stopping this process.

Source:

Journal reference:

Ma, W., et al. (2023). Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment. Nature Communications. doi.org/10.1038/s41467-023-38252-8.