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Scientists at The Wistar Institute have identified a combination treatment that overcomes two of the biggest barriers to immunotherapy in glioblastoma. In a study published in Neuro-Oncology, the researchers show that reprogramming myeloid cells, a type of immune cell that glioblastoma tumors co-opt to protect themselves, while simultaneously boosting cancer-fighting T cells shrank the tumors and prevented them from coming back.

"Immunotherapy works in many different cancer types, but the same approach has yielded only a 10% success rate in glioblastoma," said Filippo Veglia, Ph.D., assistant professor in the Genome Regulation and Cell Signaling Program at the Ellen and Ronald Caplan Cancer Center at The Wistar Institute and senior author of the study.

"Our study shows that combination therapy is paramount to making immunotherapy work for glioblastoma patients. We need to target two different populations of cells."

Glioblastoma is the most aggressive and deadly primary brain cancer in adults. Immunotherapies that have transformed care for other cancers have largely failed against it, in part because glioblastoma tumors are packed with myeloid cells—immune cells that, inside the tumor, suppress the immune system by shutting down nearby T cells that would otherwise attack the cancer.

The few functional T cells that do reach the tumors face a second problem: They become chronically active, which wears them down into a dysfunctional state called exhaustion , leaving them unable to kill tumor cells.

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