They identify cells that promote brain metastasis

Researchers from the National Center for Cancer Research (CNIO) have identified the type of cells that they take the side of cancer in cases of brain metastasespreventing the immunotherapy treatment from working, and they try treatments to suppress it.

The discovery, published in the American Association for Cancer Research’s journal Cancer Discovery, reveals solving the problem of ineffective immunotherapeutic treatment in some cases, brain metastases.

Cancer spreads through the brain when tumor cells trick the immune system and they prevent me from fighting against them.

In this sense, Immunotherapeutic treatments attempt to avoid this blockage. immune system by cancer cells, but this does not always work.

“Patients with brain metastases, that is, those who are already experiencing symptoms of metastasis, respond poorly to immunotherapy. But it is also increasingly common for patients who have responded well to immunotherapy to relapse and it is often associated with new brain metastases“explains one of the authors, Manuel Valiente, head of the brain metastases group at the CNIO.

Protumor cells

Scientists have seen it The root of the problem is the blood-brain barrierresponsible for filtering the blood entering the brain to protect it from toxins, which makes it difficult for antibodies used in immunotherapy to penetrate, making the treatment ineffective.

In particular, they identified some brain cells called astrocytes What inhibit the functioning of the immune system and prevent it from killing tumor cells.

“Pro-tumor astrocytes produce a molecule called TIMP1 it interferes with the shutdown of the protective cells that are supposed to kill cancer cells,” says another author, CNIO researcher Nable Priego.

“Until now, astrocytes have not been considered immunomodulators.neither in general studies, nor, especially, in relation to brain tumors. Our research is not only innovative from a clinical point of view, it is also very innovative for the development of scientific knowledge,” emphasizes Valiente.

Once this molecule, TIMP1, was shown to act on immune system cells and make them less effective, the CNIO team proposes use it as a biomarkerto detect brain metastases affected by this mechanism of immunosuppression.

“TIMP1 is a good biomarker because in patients with brain metastases secreted in much larger quantities in the cerebrospinal fluid,” says the researcher.

Medicine

The researchers suggested a drug called silibinin (still used for other indications), which inhibits the production of the TIMP molecule by astrocytes.

“Clinical trials are already underway to test its therapeutic efficacy in brain metastases. We hope that the results will be achieved in 2025.” says Valiente.

The goal, according to the researcher, is combine TIMP1 inhibition with traditional immunotherapy“which will increase the effectiveness of the therapeutic strategy and facilitate its inclusion in clinical protocols.”