Glioblastoma, an aggressive form of primary brain cancer, is known for its resistance to treatment, with most patients surviving for less than two years.
Researchers at the University of Notre Dame have discovered that an understudied cell type in the brain could provide insights into how glioblastoma resists immunotherapy.
Perivascular fibroblasts, a relatively new cell type found in brain blood vessels, were identified as a critical factor in glioblastoma resistance.
These fibroblasts deposit collagen to maintain brain vessels’ structural integrity and functionality in healthy individuals.
Using bioinformatics and AI-based approaches, the researchers analyzed genes expressed in the tumor microenvironment, identifying two groups of glioblastoma patients: those with a higher proportion of perivascular fibroblasts and those with significantly fewer.
Patients with more perivascular fibroblasts tended to respond poorly to immunotherapies and had worse survival outcomes.
Further investigation revealed that perivascular fibroblasts contribute to creating an immunosuppressive tumor microenvironment, enabling the cancer to evade the immune system.
These fibroblasts may also support the resistance of cancer cells to therapies like chemotherapy.
The researchers plan to conduct additional experiments to confirm their findings and explore ways to improve the response to immunotherapy in glioblastoma patients.
While perivascular fibroblasts are typically associated with a healthy brain vasculature, in the context of glioblastoma, they appear to be repurposed to support tumor growth and resistance.
The discovery of these understudied brain cells offers new avenues for research and potential treatments for glioblastoma, a highly challenging cancer to treat.
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The research findings can be found in npj Genomic Medicine.
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