Wistar team cracks glioblastoma defenses with two-pronged immune attack

By Elena MacLeod · October 8, 2026, 10:22 PM · 3 mins read

Wistar Institute researchers have shown that rewiring myeloid cells and activating T cells together can sharply extend survival in glioblastoma models, breaking through a cancer long known for resisting treatment.

Lab mice with glioblastoma rarely get a break. In most studies, tumors outmaneuver every immune trick thrown at them. This time, Wistar Institute scientists forced the cancer to blink first.

Filippo Veglia, Ph.D., and his team mapped out how glioblastoma’s oxygen-starved core turns myeloid cells into T cell saboteurs. Their findings, published in Neuro-Oncology, show that hypoxia alone pushes these immune cells into a suppressive mode. The group then used axitinib, a kidney cancer drug, at low doses to cut tumor hypoxia. That move stopped myeloid cells from shutting down T cells and let more T cells reach the tumor. Median survival in mice ticked up from 17 to 19 days. The gain was real, but modest.

Axitinib, used here in low doses to reduce tumor hypoxia, is already approved in clinical practice for advanced kidney cancer in combination with immunotherapy.

EurekAlert!

After axitinib, many T cells inside the tumor carried the 4-1BB receptor—a sign they were active but close to burning out. The team gambled on a second hit: a 4-1BB agonist to jolt these T cells back into action. The combination paid off. Median survival jumped to 42 days, and 40% of mice lived long term. When researchers reintroduced tumor cells, those survivors didn’t grow new tumors. The immune system had learned to remember and fight back, as confirmed in preclinical tests.

These results are still preclinical, but the mechanics are clear. Hypoxia triggers myeloid suppression. Timed activation of 4-1BB (CD137) can rescue exhausted CD8+ T cells. The study’s approach—targeting both myeloid and T cell arms—sets a new technical bar for solid tumor immunotherapy. Bioengineer coverage details how the 4-1BB agonist works on already activated, but tired, anti-tumor T cells.

Previous studies have also explored activating 4-1BBL+ B cells via agonistic CD40 and IFN-γ to induce anti-tumor immunity in glioblastoma, highlighting a broader research trend focused on CD40/4-1BB signaling.

Frontiers in Immunology

Veglia’s group is now moving toward clinical trials in glioblastoma patients. They are also testing whether axitinib can boost CAR T cell therapy, which has struggled in solid tumors. Hypoxia-driven immune suppression shows up in other tough cancers, including pancreatic cancer.

For a field used to setbacks, this dual strategy stands out. The Wistar team didn’t just slow the tumor—they exposed the machinery behind its resistance. Veglia summed it up: “There are no cures for glioblastoma, so this is an opportunity to make a real difference for patients.” The evidence remains preclinical. The next step is to see if these gains hold up in people.

Topics:

Translational Research Cell & Gene Therapy #CAR T cell #Tumor-infiltrating lymphocyte

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Elena MacLeod

Elena MacLeod is Clinical Biotechnology Editor at GenoMethods, covering CAR-T, engineered cell therapies, gene therapy, clinical trials, cancer immunology and regulatory developments. Her evidence-first reporting focuses on trial design, patient populations, safety, efficacy, response durability and the limitations that determine how early clinical results should be interpreted.