2024-10-02 08:05:00
A new treatment for brain metastases who do not respond or respond poorly to immunotherapy. This is what a team says National Center for Cancer Research (CNIO) in a study published in the journal ‘Cancer discovery‘ in which, furthermore, they provide a biomarker to predict in which cases to apply it.
The study goes further. The group of Manuel Valente also presents a therapeutic alternative targeting astrocytes: the combined use of immunotherapy with inhibitors that prevent the production of the TIMP1 molecule.
Our body has a mechanism to destroy everything that attacks it, be it viruses, bacteria or tumor cells: the immune system. Cancer proliferates when tumor cells trick this system, preventing it from working against them. THE immunotherapy Cancer uses drugs aimed at avoiding this blockade of the immune system by tumor cells, but immunotherapy does not always work.
In the case of brain metastases – when the tumor that arises in an organ spreads to the brain – immunotherapy has recently been tested, with mixed results.
«Brain metastases represent a serious clinical problem», explains Valiente, director of the study which is now publishing its results. «Patients with advanced brain metastases, i.e. those who already perceive the symptoms of metastases, do not respond well to immunotherapy. Furthermore, it is increasingly common for patients who have responded well to immunotherapy to relapse, and this is often due to the appearance of new metastases in the brain.
Therefore, immunotherapy with blocking antibodies does not appear to be the optimal system for brain metastases. One possible cause is the existence of the blood-brain barrier, a type of permeable membrane that filters blood entering the brain to defend it from toxins. But this vascular barrier also makes it difficult for antibodies used in immunotherapy to enter. Without antibodies, immunotherapy doesn’t work.
Astrocytes
The group discovered it – he explains Neibla Priegofirst signatory of the article – that a type of brain cells called astrocytes act as immunomodulators, that is, they interact with the brain’s immune system, and in the case of brain metastases they abuse this function because they are influenced by the tumor.”
Perverted by cancer, astrocytes take the side of tumor cells when there are brain metastases. The interaction of astrocytes with the immune system, something that should be a normal process of immunomodulation, becomes a mechanism that fuels cancer, because astrocytes make it difficult for defensive cells to work and prevent them from killing tumor cells.
The CNIO group has identified a key molecule in the process, called TIMP1. “Pro-tumor astrocytes produce TIMP1, and this protein is involved in disabling defensive cells that are supposed to kill tumor cells,” says Priego.U
The goal is to combine TIMP1 inhibition with traditional immunotherapyP
Once it has been demonstrated that this molecule, TIMP1, acts on the cells of the immune system, making them more ineffective, the CNIO team proposes using it as a biomarker to identify brain metastases affected by this mechanism of immunosuppression.
The study goes further. Manuel Valiente’s group proposes a therapeutic alternative aimed at astrocytes: the combined use of immunotherapy with inhibitors that prevent the production of the TIMP1 molecule.
«There is a drug called silibininwhich has already been used in compassionate use, which inhibits the production of the TIMP molecule”, says Valiente. «There is already an ongoing clinical study to test its therapeutic efficacy in brain metastases. “We hope to have the results in 2025”.
The goal is to combine TIMP1 inhibition with traditional immunotherapy, “which would increase the potency of the therapeutic strategy and facilitate its incorporation into clinical protocols,” Valiente says.
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