In the last few decades, the medical field has been abuzz with excitement about the promise of immunotherapy to treat cancer. In 2018, the Nobel Prize recognized James P. Allison and Tasuku for their groundbreaking discovery of cancer therapy by inhibiting negative immune regulation. In 2022, CAR T cell therapy, the process of reengineering a patient's own immune cells to attack cancer, was approved by the FDA to treat blood cancer and showed promise for other types of cancers.
But despite all its dazzling potential, one type of brain cancer has stubbornly refused to respond to immunotherapy treatment – malignant meningiomas. Meningiomas are a form of brain cancer that affect 37,020 Americans every year and currently defy conventional cancer treatments. Even surgery merely buys the patient time, and most of these meningiomas recur after surgery. This is especially worrisome for the 10-15% of cases that are malignant.
Jacky Yeung, MD, assistant professor at Yale School of Medicine, is looking for a way to harness the power of immunotherapy for meningiomas.
For immunotherapy to work, immune cells must be able to “crawl” through the vessel wall into the tumor, says Dr. Yeung. In 2021, Dr. Yeung published an article in Neuro-oncology with Lieping Chen, MD, PhD, immunologist at Yale School of Medicine that showed that malignant meningiomas did not respond to conventional immunotherapy. While normal blood vessel cells express proteins that make it easy for immune cells to attach, tumor blood vessels in meningiomas do not express those adhesion molecules.
“Unlike lung cancers and melanoma, which immunotherapy has proven to be an effective treatment, the same strategy to boost immunity isn’t effective for meningioma if the immune cells can’t even get into the tumor,” says Dr. Yeung. “They do not express molecules that immune cells can stick to. It’s like they’re going straight by the train station and not stopping.”
Recently, he was awarded a grant from the American Brain Tumor Association to explore a novel proposition – targeting a molecule in brain tumor blood vessels to make them behave more normally.
Dr. Yeung's current work with Dr. Chen focuses on a gene, CD93, that could be the key to turning tumor vessel wall cells into non-cancer vessel wall cells, which should theoretically make the tumors more susceptible to attack by our immune system.
The grant would enable Dr. Yeung to test this gene in pre-clinical mice models and study whether the target is present in human tumor samples.
"Patients with high grade meningiomas have to go through surgery and radiation with no other effective medical treatments available, it is the hope that through this research we'll be able to unleash the power of our own immune system to treat these difficult tumors," says. Dr. Yeung.