Recurrent high-grade astrocytomas (including glioblastoma and IDH-mutant grade 3 and 4 astrocytomas) remain one of the toughest challenges in brain cancer treatment. Even after surgery, radiation, and chemotherapy with temozolomide, the options available when the disease returns provide only limited benefit, and survival rates are very poor. This makes the search for new therapies urgent.
Immune checkpoint inhibitors (ICIs), such as pembrolizumab and nivolumab, have revolutionized treatment for many cancers by activating the body’s T cells. But in high-grade astrocytomas, ICIs have not improved survival, whether used alongside standard treatment or combined with drugs like bevacizumab after recurrence.
Laser interstitial thermal therapy (LITT), a minimally invasive surgery that reduces tumor size, may help prepare recurrent high-grade astrocytomas to respond better to immune checkpoint inhibitors.
Researchers at Keck Medicine of USC may have found a way to cross the blood-brain barrier and make immune checkpoint inhibitors work for patients with recurrent high-grade astrocytoma. This breakthrough could help extend lives.
AI to predict brain cancer outcomes
A phase 1/randomized phase 2b trial was designed to test the combination of the immune checkpoint inhibitor pembrolizumab with LITT in patients with rHGA.
Forty-five patients enrolled in the study. All trial participants were in their second recurrence of astrocytoma, with nearly 15% in their third recurrence, meaning the cancer was at a very advanced stage.
Researchers found something remarkable. When patients were treated using laser interstitial thermal therapy (LITT) followed by the immunotherapy drug pembrolizumab, almost half were still alive 18 months later.
By contrast, patients who had the standard surgery plus pembrolizumab didn’t survive that long; none made it to 18 months.
Even more striking, about one in three patients lived beyond three years with the LITT-plus-immunotherapy approach. That’s a huge leap compared to the usual survival of just four to five months for people with recurrent high-grade astrocytoma.
David Tran, MD, PhD, chief of neuro-oncology with Keck Medicine, said, “These results suggest that LITT can help the immune checkpoint inhibitor pembrolizumab work more effectively against high-grade astrocytoma. Patients with this type of advanced cancer have few remaining options and poor outcomes, and this approach could meaningfully extend their survival time and provide new hope for patients and their loved ones.”
New method targets aggressive brain tumor
A previous study has suggested that LITT-induced heat can disrupt the blood–brain barrier for several weeks. For several weeks, the barrier stays open just enough for T-cells, the body’s cancer-fighting soldiers, to march in and do their job once they’ve been activated by pembrolizumab (an immune checkpoint inhibitor).
In the trial, patients were assigned to receive either LITT or traditional surgery/biopsy, followed by pembrolizumab. For those with LITT, neurosurgeons used MRI as a map to guide a laser probe directly into the tumor. The laser heat destroyed the cancer while carefully sparing healthy brain tissue, and, as a bonus, it broke down the barrier, giving the immune system a clear shot at the enemy.
Laser therapy (LITT) activates a special group of immune cells called non-classical monocytes. At the same time, pembrolizumab boosts the army of CD8⁺ T cells, helping them multiply, expand, and build long-term memory for fighting the tumor.
Together, this combo (LITT + pembrolizumab) looks safe and powerful. It may break through the usual immune “shut‑down” seen in recurrent high‑grade astrocytoma, giving the body a real chance to mount an effective anti‑tumor defense.
Journal Reference:
Campian, J.L., Le, S.B., Ghiaseddin, A. et al. Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial. Nat Commun 17, 1763 (2026). DOI: 10.1038/s41467-026-69522-w