Scientists at Northwestern University have discovered a biological mechanism in which specialized immune cells within glioblastoma tumors metabolize fructose to suppress immune responses and promote tumor growth. Published in the Proceedings of the National Academy of Sciences, the study is the first to identify this sugar pathway as a driver of immune suppression in brain tumors.
New Sugar Pathway Target Identified in Glioblastoma
Glioblastoma remains the most common and aggressive primary brain tumor in adults, maintaining a five-year survival rate of less than 7%, according to the National Brain Tumor Society, as reported by Northwestern. The tumor microenvironment includes immunosuppressive myeloid cells originating from the bone marrow and brain-resident microglia, which normally protect the central nervous system.
We knew microglia use this fructose transporter as part of their normal biology, but we did not expect it to be this important for brain tumor growth,
said Jason Miska, study senior author and assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine. Miska noted that across several mouse models, removing the fructose transporter resulted in tumors that simply did not grow.
Dual-Targeting Immunotherapy Strategy and AI Radiation Planning
Separately, researchers at McMaster University developed an immunotherapy strategy targeting both brain tumors and the immune cells that support them. Published in McMaster, the study focuses on glioblastoma hijacking macrophages. Researchers identified Glycoprotein non-metastatic melanoma protein B (GPNMB) on cancer cells and tumor-supporting macrophages, allowing Chimeric Antigen Receptor T-cell (CAR-T) therapy to recognize GPNMB and attack the tumor on multiple fronts.
Instead of treating the tumour as only a mass of cancer cells, we suggest that we must treat glioblastoma as a connected tumour-immune ecosystem,
said Sheila Singh, senior author and professor of surgery at McMaster, as detailed by McMaster. Pre-clinical models using this therapy eliminated detectable tumors and achieved long-term disease-free survival.
In clinical radiation research, a study published May 13 in Nature Communications tested a method using artificial intelligence to predict where glioblastoma is likely to return. As reported by ChristianaCare, researchers used advanced MRI scans and machine learning to map hidden cancer cells and deliver higher radiation doses to high-risk spots in 20 newly diagnosed patients.
At the MIT Koch Institute for Integrative Cancer Research, a team led by Forest White used immune profiling tools to map how macrophages evolve into a protective shield for tumors. Described by MIT, researchers isolated cell surface antigens from glioblastoma and macrophage cells using liquid chromatography and mass spectrometry. The team identified over 800 peptides in macrophages and over 40 Rho GTPase-associated antigens with increased expression in co-cultured glioblastoma cells.
While these preclinical and early clinical findings offer potential paths forward, researchers emphasize that transitions to broader human trials require careful validation. Plans are underway to test the AI radiation approach through the NRG Oncology network, while the cellular and metabolic targets identified at Northwestern, McMaster, and MIT establish a foundation for future combination therapies.
