Blocking immune cell lipid signals may contain glioblastoma before surgery

Researchers at the VIB-KU Leuven Center for Cancer Biology have reported a way to make glioblastoma, the most aggressive primary brain tumor in adults, less invasive by interrupting communication between the brain’s immune cells and tumor cells. The study, published in Cancer Cell, found that blocking specific lipid signals released by microglia reduced the spread of tumors in mouse models, raising the possibility of treating patients before surgery to make their tumors more contained and easier to remove.

Glioblastoma carries a median patient survival of about 15 months, and its danger lies in how tumor cells spread into the surrounding brain tissue. This infiltration prevents the complete surgical removal of the tumor, and total resection is the strongest predictor of survival. Finding ways to contain the tumor before an operation could therefore be an important strategy to extend patients’ lives, the researchers note.

The team, led by Professor Gabriele Bergers, studied the interaction between tumor cells and microglia, the immune cells of the brain. Microglia are known to promote glioblastoma progression by secreting certain proteins that tumor cells can use to grow, but the role of lipids, or fatty molecules, in this process had remained largely unexplored until now.

Using mouse models and tissue from glioblastoma patients, the researchers found that tumor cells use lipids released by microglia to become more mobile and invade healthy areas of the brain. “We found that microglia release a specific type of lipid called lysophosphatidic acids (LPAs) that binds to tumor cells, activating pathways that help them spread to further areas of the brain,” explains first author Dr. Carla Pallarés-Moratalla of the VIB-KU Leuven Center for Cancer Biology.

Building on this discovery, the researchers investigated whether blocking this interaction could make tumors less invasive, and it did. “We were able to interrupt these signals and make tumors less invasive,” says Pallarés-Moratalla. Importantly, although the size of the tumor did not change, the results raise the possibility of treating patients before surgery to make their tumors more contained and easier to remove. Because the approach limits spread but does not shrink the tumor, the authors suggest it could be combined with therapies that reduce tumor size, which could further improve patient survival.

The researchers also looked for the same patterns in human samples. Tests on patient-derived tumor cell lines showed that immune cells promoted invasion in the same way as in mice. “It was rather surprising to see how closely the mechanism we found in mice was reproduced in human glioblastoma, which suggests the findings could translate to patients,” says Pallarés-Moratalla.

The authors stress that these are still early findings, although the discovery opens the door to a new way of approaching treatment. The work is described as an experimental study, with animals as the subject of research, and human validation so far rests on patient-derived cell lines and tissue samples rather than clinical trials.

One feature of the strategy may make it broadly applicable. “Glioblastoma tumors are very heterogeneous, meaning that in the same patient, different areas of the tumor can carry different mutations,” explains Professor Bergers. “But our approach does not target the genetic makeup of the tumor cells – it instead targets the communication between immune and cancer cells, which makes it applicable to a broader spectrum of glioblastoma.”

By targeting the lipid-mediated dialogue between microglia and tumor cells rather than the tumor’s own mutations, the study points to a therapeutic vulnerability that could, in principle, complement existing surgical and drug-based approaches. The researchers emphasize that further work will be needed before such a strategy reaches patients, but the finding offers a new direction for a disease that has long resisted treatment.

Subject of Research: How microglia lipid signaling drives glioblastoma invasion and can be blocked to contain tumors

Article Title: How blocking immune cell signals could make brain tumors easier to remove

Article References: How blocking immune cell signals could make brain tumors easier to remove. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: glioblastoma, microglia, lysophosphatidic acid, lipid signaling, tumor invasion, brain tumor surgery, VIB-KU Leuven, Cancer Cell, tumor microenvironment, pre-surgical treatment, blocking, immune