Immunotherapy Shows Promise for Meningioma Treatment by Targeting STING Pathway

Northwestern Medicine scientists have identified a promising immunotherapy approach for meningiomas, the most common type of primary brain tumor. The research, published in Nature Communications, centers on activating the STING (Stimulator of Interferon Genes) pathway to trigger both cytotoxic and immune responses against the tumor.

Meningiomas affect more than 39,000 Americans annually, originating from the meninges—the protective membranes covering the brain and spinal cord. While surgery and radiation are often effective, advanced and aggressive tumors can be therapy-resistant and prone to recurrence. Currently, there are limited systemic therapies consistently effective for meningiomas, leading to growing interest in immunotherapy.

The Role of the STING Pathway

The research team analyzed single-cell RNA sequencing data from 22 patients with meningioma tumors. Their analysis revealed that the STING pathway, known for its role in supporting anti-tumor immunity, is expressed not only within immune cells in the tumor microenvironment but also within the meningioma tumor cells themselves. This is a key distinction from other brain tumors like gliomas.

“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,” explained Dr. Mark Youngblood, a resident physician in neurological surgery and lead author of the study. “This provides an opportunity to target both immune and tumor cells directly in patients, and also represents a model to understand more about STING’s role in cell death.”

Experimental Drug Shows Positive Results

Researchers administered an experimental drug, STING agonist 8803, to human meningioma tumor samples obtained during surgery. Previous research led by Dr. Heimberger had demonstrated that 8803 could reprogram suppressed immune responses in glioblastoma.

In the meningioma samples, 8803 inhibited tumor growth and promoted the death of tumor cells. These findings were replicated in mouse models, with the drug also activating latent immune populations and reducing tumor volume, and mortality.

Mechanism of Action: Programmed Necrosis and Immune Activation

Further investigation using RNA sequencing and electron microscopy revealed that the STING agonist triggers programmed necrosis, a form of cell death, within the tumor cells. This process activates the Gasdermin D protein, creating pores in the cell membrane and causing an uncontrolled release of antigens. This release sparks an inflammatory response and further immune activation.

“It’s a particularly dirty type of cell death and, we suppose that it synergistically triggers even more immune activation,” Dr. Youngblood stated.

Collagen Reduction and Tumor Mass Decrease

Meningioma tumors are often characterized by a large amount of collagen, contributing to their bulk and potential to cause brain compression. The study found that treatment with the STING agonist reduced collagen production by tumor cells. Simultaneously, immune cells increased the production of collagen-degrading enzymes, leading to an overall reduction in tumor mass.

“We’re hoping that in addition to arresting the growth of the tumor and causing the death of the tumor cells, we actually might notice a lot of the bulk of the tumor reduced through this extracellular matrix degradation,” Dr. Youngblood added.

Clinical Implications and Future Research

These findings suggest that targeting the STING pathway with STING agonist 8803 could be an effective strategy for inducing both direct tumor cell death and a robust inflammatory immune response in meningioma. The study also provides a valuable model for understanding the broader role of the STING pathway in various diseases, extending beyond cancer.

The research is being conducted at the Lou and Jean Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, a nationally recognized leader in brain tumor treatment and research. The institute offers patients individualized care and access to advanced clinical trials. Learn more about meningioma treatment at Northwestern Medicine.

Reference: Youngblood MW, Tripathi S, Najem H, et al. STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways. Nat Commun. 2026. Doi: 10.1038/s41467-026-69296-1