Pre-surgery immunotherapy may improve treatment for deadly brain cancer
· Medical Xpressedited by Sadie Harley, reviewed by Robert Egan
Sadie Harley
Scientific Editor
Meet our editorial team
Behind our editorial process
Robert Egan
Senior Editor
Meet our editorial team
Behind our editorial process Editors' notes
This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:
fact-checked
peer-reviewed publication
trusted source
proofread
The GIST Add as preferred source
With a five-year survival rate of barely 5%, glioblastoma remains one of the deadliest brain cancers. First-line treatment consists of surgery to remove as much tumor tissue as possible.
A team from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) has now shown that this operation triggers a tissue-repair process that makes the residual tumor even harder to combat. By administering lab-engineered immune cells—CAR-T cells—to mice before rather than after surgery, the team achieved unprecedented durable tumor control.
This research, with significant clinical implications, is published in the journal Nature Communications.
CAR-T cell therapies consist of collecting a patient's own immune cells and engineering them in the laboratory so they can recognize, engage and eliminate tumor cells.
Until now, clinical trials testing CAR-T cells against glioblastoma have aimed to administer them after surgery, the first-line intervention.
"However, the surgical procedure itself is not neutral, neither for the immune system nor for the tumor microenvironment, which will seek to defend the tumor against this assault," explains Denis Migliorini, associate professor in the Department of Medicine and at the Translational Research Center in Onco-Hematology (CRTOH) of the UNIGE Faculty of Medicine, and head of the HUG Neuro-oncology Unit, who led the research.
"We therefore wanted to investigate, on the one hand, whether administering CAR-T cells before surgery changed treatment efficacy and, on the other, whether we could identify the most effective markers of immunosuppression."
A scar that protects the tumor
Using two mouse models closely replicating the human disease, the scientists analyzed the immune mechanisms at work in the tumor microenvironment with and without surgery, as well as their impact on tumor recurrence.
"The tissue-repair mechanism that sets in after surgery leads to the overexpression of the TREM2 protein, a marker of immunosuppressive macrophages that is very strongly expressed in the tumor microenvironment. This protein reflects their level of activity and their ability to dampen the antitumor immune response," explains Martin Pédard, senior research and teaching assistant in Migliorini's team.
"Thus, TREM2, already overexpressed in the tumor before surgery, further increases in response to the surgically induced wound and triggers a massive macrophage response that neutralizes the immune cells fighting the cancer."
So, could the infusion of CAR-T cells before rather than after surgery help avoid this hostile postoperative environment? The team set out to test this hypothesis. They also developed CAR-T cells specifically targeting TREM2 that were delivered directly into the cavity during surgery in a mouse model.
Combined with another type of CAR-T cell targeting tumor cells via the specific marker GD2, these cells were able to neutralize the immunosuppressive macrophages.
Unprecedented control over the tumor
Administered before rather than after surgery, GD2-targeting CAR-T cells retained their ability to attack the tumor and achieved far better disease control. Combined with the TREM2-targeting CAR-T cells delivered into the resection cavity, they further extended survival.
"CAR-T cells shift the tumor toward an environment more favorable to the immune response, with more molecules promoting inflammation and tumor cell death," Migliorini says.
The team then confirmed these observations in human tissue. Using a platform developed with the HUG neurosurgery and neuropathology divisions, they were able to culture tumor samples taken directly in the operating room and reproduce, in this tissue, the effect observed in mice.
Toward clinical trials
These results could influence the design of future clinical trials. The Geneva team plans to open a first-in-human Phase I trial in 2027 for newly diagnosed patients. "This trial primarily aims to demonstrate the safety of CAR-T cells after surgery and radiochemotherapy," Migliorini says. "Based on our data, we will then be able to modify the protocol to include a trial in which CAR-T treatments would be administered before surgery."
Publication details
Martin Pedard et al, Perioperative myeloid cell remodeling shapes CAR-T cell efficacy in glioblastoma, Nature Communications (2026). DOI: 10.1038/s41467-026-76206-y
Journal information: Nature Communications
Key medical concepts
GlioblastomaChimeric Antigen Receptor T-cells
Clinical categories
OncologyNeurology Provided by University of Geneva Who's behind this story?
Sadie Harley
BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →
Robert Egan
Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →
Citation: Pre-surgery immunotherapy may improve treatment for deadly brain cancer (2026, September 2) retrieved 2 September 2026 from https://medicalxpress.com/news/2026-09-pre-surgery-immunotherapy-treatment-deadly.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.