Anew weapon against glioblastoma, one of the most aggressive and difficult-to-treat brain tumours, has been developed by a team from the Neurological Institute of Milan, which has launched a study published in Nature Communications by harnessing the immune defences of patients.
    The team of researchers, led by Serena Pellegatta, have exploited tumour-infiltrating T lymphocytes.

These cells of the immune system are present in glioblastoma, but are few and often "exhausted," therefore poorly functional.
    The method the team developed isolates and expands in the laboratory - specifically and tailored to the patient - functional and reactive tumor infiltrating T lymphocytes (tr-TIL), maintaining their immune memory intact.
    These lymphocytes, once reinfused, are therefore potentially capable of recognizing and eliminating tumor cells.
    Researchers have also discovered a new mechanism capable of unmasking the tumor.
    By blocking the PD-L1 protein, which glioblastoma uses to "hide" from the immune system, tr-TILs become even more functional and effective in destroying tumor cells.
    BESTA's new protocol begins with the material removed during surgery.
    Neurosurgeons collect the tumor tissue, including immune cells, with a special instrument: the ultrasonic dissector.
    Subsequently, in the laboratory, they isolate the "reactive" T lymphocytes, identified by the CD137 marker, and culture them in the presence of specific factors that promote their expansion and preserve their immune memory and functionality.
    The study involved 161 patients diagnosed with diffuse glioma.
    In laboratory tests, tr-TILs, successfully expanded from patients' tumors, were administered to animal models, resulting in a slowing of tumor growth in 70% of the animals, with a corresponding increase in survival.
    The protocol has already been adapted to Good Manufacturing Practices (GMP) standards, a fundamental requirement for clinical use, and the next step will be the initiation of the ReacTIL clinical trial, which will test the safety and efficacy of this therapy in patients with glioblastoma.
    If the results are confirmed, a new personalized strategy for the treatment of glioblastoma will be available to patients, "addressing," as Besta emphasized, "one of the most difficult challenges in oncology".
    "Our study," summarized Pellegatta, director of the Department of Neurosurgery at the Besta Hospital and the School of Specialization in Neurosurgery at the University of Milan, "demonstrates that tr-TIL therapy has the potential to become a concrete option for patients with glioblastoma." "Immune-based tumor treatment strategies are extremely interesting because they aim to exploit the body's own resources that are evidently neutralized by the disease.
    This concept has proven successful against some systemic tumors," added Francesco Di Meco, Director of the Department of Neurosurgery at Besta Hospital and of the School of Specialization in Neurosurgery at the Statale University, "but it has not shown efficacy against glioblastoma, a tumor that, unfortunately, we are unable to effectively combat to date.
    "The study led by Dr.

Pellegatta, which we published in Nature Communications, appears to identify an effective strategy for attacking glioblastoma cells and lays the foundation for immediate clinical application with the aim of offering our patients real prospects for effective treatment."
   

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