Researchers at the CNIO found that cancer manipulates specific brain cells, called astrocytes, to produce a protein that helps tumors. A drug called silibinin can block this protein and, when used with immunotherapy, may improve treatment for brain metastases.
A clinical trial is testing this. The study, published in Cancer Discovery, also suggests a way to predict when this treatment might work.
Brain metastasis happens when cancer spreads from another organ to the brain. Immunotherapy has been used to treat it, but the results have been mixed. Patients with advanced brain metastases often don’t respond well, and even those who do can relapse with new brain tumors.
A fundamental problem is the blood-brain barrier, which blocks antibodies needed for immunotherapy to work effectively in the brain.
Researchers at CNIO have found that specific brain cells, called astrocytes, can help cancer grow in the brain. Typically, astrocytes support the immune system, but cancer changes them in brain metastasis.
Instead of helping the body fight the tumor, these astrocytes protect the cancer by stopping immune cells from killing the tumor cells. This discovery could lead to new ways to treat brain metastasis.
Researchers at CNIO discovered that a protein called TIMP1, produced by astrocytes in the brain, weakens the immune system’s ability to fight cancer. This protein can be a biomarker to identify brain metastases where immunotherapy won’t work well.
TIMP1 is found in higher amounts in the cerebrospinal fluid of patients with brain metastases, helping doctors detect this issue early.
Researchers are testing a new treatment that targets astrocytes to fight brain metastasis. A drug called silibinin blocks the production of the harmful TIMP1 molecule, which helps cancer spread.
Scientists hope for the drug’s effectiveness by combining it with immunotherapy effectiveness. A clinical trial is underway, and results are expected by 2025 to see if this approach works better for treating brain metastasis.
The research highlights the critical role of astrocytes in brain metastasis. Researchers discovered that only specific subtypes of astrocytes harm patients by helping cancer spread. This is new because astrocytes weren’t previously seen as part of the immune response or involved in brain tumors.
The study is valuable for clinical progress and scientific knowledge, and it received funding from various national and international organizations.
Journal reference:
- Neibla Priego, Ana de Pablos-Aragoneses, et al., TIMP1 mediates astrocyte-dependent local immunosuppression in brain metastasis acting on infiltrating CD8+ T cells. Cancer Discovery. DOI: 10.1158/2159-8290.CD-24-0134.