STING agonist 8803 shows anti-tumor activity in meningioma study

Northwestern Medicine scientists have discovered a potent immunotherapy approach for treating meningiomas, the most common type of primary brain tumor, according to a study published in Nature Communications. In human meningioma tumor samples and mouse models, an experimental drug that activates the STING pathway, called STING agonist 8803, inhibited tumor growth, promoted cytotoxicity of the tumor cells, and reduced tumor volume and mortality in the mice.

More than 39,000 Americans are diagnosed with meningioma each year, according to the National Brain Tumor Society. While some meningiomas can be treated effectively with surgery and radiation, more advanced and aggressive tumors are therapy-resistant and can recur with increased rates of morbidity or mortality. “There are no systemic therapies shown to be consistently effective for meningiomas, and there is growing interest to use immunotherapies for targeting these tumors,” the study’s lead author said.

In the current study, the investigators sought to identify new immunotherapy targets for meningiomas by analyzing single-cell RNA sequencing datasets encompassing data from 22 patients diagnosed with meningioma tumors. From this analysis, the scientists discovered that the STING pathway is expressed both within the meningioma tumor cells and in the immune cells circulating within the tumor microenvironment. “STING is actually expressed in the meningioma tumor cells themselves and not just in the infiltrative immune populations, which is unique from other types of brain tumors such as gliomas,” the lead author said.

Next, the investigators administered STING agonist 8803 in human meningioma tumor samples harvested directly from the operating room. In the meningioma samples, the investigators found that 8803 inhibited tumor growth and promoted cytotoxicity of the tumor cells. This finding was duplicated in mouse models of meningioma, in addition to expected activation of latent immune populations.

To identify the cellular mechanisms promoting cytotoxicity in meningioma tumor cells, the scientists used RNA sequencing and electron microscopy to study meningioma tumor cells that had been treated with the STING agonist. They discovered the drug triggers programmed necrosis pathways and activates the Gasdermin D protein, which creates “pores” in the tumor cell membrane. The lack of membrane integrity triggers an abrupt and uncontrolled form of cell death which releases antigens into the tumor microenvironment, causing an inflammatory response.

Compared to other solid tumors, meningioma tumors harbor large amounts of collagen, which makes up much of the lesion’s bulk and can cause a mass effect on the brain. In meningiomas treated with the STING agonist, tumor cells showed a decrease in the production of collagen, while infiltrative immune populations increased the production of collagen-degrading enzymes, causing an overall reduction in the tumor mass.

The findings highlight the widespread expression of the STING pathway in the meningioma tumor microenvironment and suggest that using STING agonist 8803 to target this pathway may be an effective approach for inducing direct tumor and inflammatory immune responses in meningioma. Publication details listed the study as: “STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways,” published in Nature Communications with DOI: 10.1038/s41467-026-69296-1.