Anti-swelling drug may weaken immune system in brain cancer patients

Swelling caused by brain cancer is a serious problem that can lead to serious side effects and even death. While controlling swelling is important, a new study shows that a commonly prescribed anti-swelling drug suppresses the immune system for weeks after dosage, inhibiting the body's ability to fight the cancer. 

An international team of scientists from Canada and the United States looked at myeloid cells in brain cancer patients. These cells make up a large part of brain cancer tumors and have been shown to play a role in immunosuppression. The researchers used single-cell and spatial transcriptomics on myeloid cells from over 100 brain tumors to learn how they affect immune response to cancer. Single-cell transcriptomics reveal how RNA is expressed in a cell, hinting at its function, while spatial transcriptomics reveals how these cells are positioned within the tissues. 

The researchers discovered a consistent organization of cells within brain cancer, where each type of myeloid cell was found in specific areas tailored to its role. 

Notably, they found two types of immunosuppressive myeloid cells in the tumors: one linked to areas of dead tissue while the other linked to anti-swelling therapy. In patients who had been given dexamethasone, these cells had a significantly higher immunosuppressive effect than those who had not, and the effect was stronger as the dosage increased. 

Scientists then exposed otherwise non-immunosuppressive myeloid cells to dexamethasone and found that they quickly became immunosuppressive. The effect was long-lasting, remaining weeks after the drug was last given. 

In some cancer patients, doctors prescribe treatments that strengthen the body's immune response to the malignant cells, using them to fight the cancer. This study shows that dexamethasone, a drug commonly prescribed in all brain cancer patients, may be inhibiting that response, even if that drug was last given weeks before immunotherapy begins. 

Doctors should ask themselves if dexamethasone is truly needed in each case its prescribed. It is important to balance the need to reduce swelling with the need for a healthy immune response. We need to start developing alternatives to dexamethasone that do not inhibit immune response in patients." 

Dr. Charles Couturier, neurosurgeon-scientist at The Neuro (Montreal Neurological Institute-Hospital) of McGill University and one of the study's lead authors

The paper, entitled "Programs, Origins, and Immunomodulatory Functions of Myeloid Cells in Gliomas", was published in the journal Nature on Feb. 26, 2025. It was funded by the Canadian Institutes of Health Research, Fonds de recherche du Québec – Santé, the National Institutes of Health, and the Koch Institute for Integrative Cancer Research.