By Elodie Vaz | Published on March 9, 2026 | 3 min read
High-grade
astrocytoma, which includes glioblastoma, is among the most aggressive brain
tumors. Its rapid growth and strong tendency to recur after surgical resection
make it a disease with a poor prognosis. In the event of recurrence, median
survival is generally only four to five months.
While
immune checkpoint inhibitors have transformed the management of many solid
tumors by reactivating T lymphocytes against tumor cells, their effectiveness
remains limited in brain tumors. The main reason is the blood–brain barrier.
Crossing
the blood–brain barrier
Researchers
at Keck Medicine of USC in California explored a strategy designed to overcome
this barrier in order to enhance the effect of an immune checkpoint inhibitor,
pembrolizumab, in patients with recurrent high-grade astrocytoma. The results
were published on February 26 in the journal Nature Communications.
The
hypothesis was to combine laser interstitial thermal therapy (LITT)—a minimally
invasive procedure that destroys tumor tissue through hyperthermia—with
immunotherapy, in order to facilitate T-cell infiltration and activation within
the tumor. The Phase 1/2b clinical trial enrolled 45 patients experiencing a
second recurrence of high-grade astrocytoma. Nearly 15% were in a third
recurrence, reflecting very advanced disease.
Laser
interstitial thermal therapy
Participants
were assigned to two approaches: either laser interstitial thermal therapy
(LITT) or surgery with biopsy, followed in both cases by pembrolizumab
treatment.
For LITT,
neurosurgeons used MRI to precisely locate the tumor, guide the laser probe,
and deliver heat in a targeted manner. The hyperthermia destroys tumor tissue
while preserving surrounding healthy structures and, crucially, disrupts the
blood–brain barrier for several weeks.
According
to the team’s previous work, this time window may allow T cells activated by
pembrolizumab to enter the brain and exert cytotoxic activity.
The
reported data are striking. Nearly half of the patients treated with LITT
followed by pembrolizumab were still alive 18 months after treatment. By
contrast, none of the patients who received the conventional treatment (surgery
followed by pembrolizumab) were alive at 18 months.
More than
one third of patients in the LITT–immunotherapy group survived beyond three
years, far exceeding the expected four to five months of survival for recurrent
high-grade astrocytoma.
Disruption
of the blood–brain barrier appears to play a central role. “This alerts T cells
to the presence of the tumor and facilitates their migration to the tumor to
locate and attack it,” explained Professor David Tran, MD, PhD, head of
neuro-oncology at Keck Medicine, co-director of the USC Brain Tumor Center, and
senior author of the study, in a press release.
Lifting
the brain’s immune lock
He
emphasized the potential clinical significance of these findings. “They suggest
that LITT can enhance the effectiveness of the immune checkpoint inhibitor
pembrolizumab against high-grade astrocytoma. Patients with this type of
advanced cancer have few therapeutic options and a poor prognosis. This
approach could significantly extend their life expectancy and offer new hope to
patients and their loved ones.”
As the U.S.
Food and Drug Administration has since authorized LITT for certain brain
tumors, and pembrolizumab is already approved in multiple oncology indications,
these results pave the way for larger-scale trials. They also encourage
exploration of other combinations aimed at modulating the blood–brain barrier
to optimize intracranial immunotherapy.
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.
