Health. Brain Cancer: Study Could Revolutionize Immunotherapy

Immunotherapy has revolutionized the treatment of many cancers. This therapy stimulates or modifies the patient's immune system so that it specifically recognizes and attacks cancer cells.

However, the brain tumors , such as gliomas (the type of brain cancer The most common and aggressive primary type), are particularly difficult to treat, partly because they strongly inhibit the patient's immune system responses.

New findings published in Nature by researchers at the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute in Boston, Massachusetts, could make immunotherapies for brain cancer more effective.

Groups of genes that activate or inhibit the human immune system

The team analyzed nearly 200,000 immune cells , called myeloid cells, from tumor samples of glioma patients. Myeloid cells make up up to half of the cells in many brain tumors.

To do this, the scientists used single-cell RNA sequencing, which analyzes the gene expression of individual cells. They were able to identify four gene expression "programs"—sets of genes with coordinated activity—that either suppress the immune system or activate it. Two of these programs were inflammatory, with the immune system being activated and potentially attempting to attack the tumor.

The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.

The team says defining and understanding what drives these programs could ultimately help researchers target them with new drugs to modulate parts of the immune system and improve patients' response to immunotherapy.

"This study provides us with the data needed to create strategies targeting myeloid cells to modulate these programs and make immunotherapies more effective in patients with brain tumors," said Tyler Miller, co-author of the study.

These newly discovered genetic signatures provide a roadmap that the scientific community can use to study myeloid cells and their impact on how brain tumors respond to treatment.

The researchers also created organoids—three-dimensional assemblies of cells in the lab—from pieces of patient tumors. They treated them with dexamethasone (a drug commonly used for brain tumors before moving on to immunotherapy).

Wake up the immune system

They found that myeloid cells within the organoids continued to express immunosuppressive programs long after the drug was removed, suggesting that this steroid could affect the response to immunotherapy.

Using the organoids, the researchers also discovered that certain molecules (inflammatory protein IL-1β, growth factor TGF-β) caused the tumors to express the other immunosuppressive program.

The goal for scientists in the coming years? To manipulate these four crucial gene programs with drugs to make immunotherapies more effective. And to reawaken the immune system.