Understudied Cell in the Brain Could Be Key to Treating Glioblastoma

Glioblastoma is one of the most treatment-resistant cancers, with those diagnosed surviving for less than two years.

In a new study in NPJ Genomic Medicine, researchers at the University of Notre Dame have found that a largely understudied cell could offer new insight into how the aggressive, primary brain cancer is able to resist immunotherapy.

Using standard bioinformatics and newer AI-based approaches, Datta’s TIME Lab began analyzing different genes expressed in the tumor microenvironment related to the extracellular matrix — or the scaffolding cells create to support future cell adhesion, migration, proliferation and differentiation — and other various cell types.

What they found was a surprising, fairly new cell type: perivascular fibroblasts.

These fibroblasts are typically found in the blood vessels of a healthy brain and deposit collagen to maintain the structural integrity and functionality of brain vessels.

In their data, researchers were able to identify two groups of patients: those with a higher proportion of perivascular fibroblasts and those with significantly less.

They found that brain cancer patients with more perivascular fibroblasts in their tumors were more likely to respond poorly to immunotherapies and have poor survival outcomes.

When exploring how this is possible, the researchers found that perivascular fibroblasts support the creation of an immunosuppressive tumor microenvironment, allowing the cancer to better evade the immune system.

The fibroblasts may also help the cancer resist therapies — such as chemotherapy that targets dividing cells — by promoting stem-like cancer cells that rarely divide, which are believed to be a major source of tumor relapse and metastasis.

Because perivascular fibroblasts are a part of a healthy brain’s vasculature, Datta believes that these cells are breaking off and getting close to or infiltrating the glioblastoma tumor.

However, instead of supporting healthy brain function, these fibroblasts are getting reprogrammed and helping the tumor instead.

Sources:

Maksym Zarodniuk, Alexander Steele, Xin Lu, Jun Li, Meenal Datta. CNS tumor stroma transcriptomics identify perivascular fibroblasts as predictors of immunotherapy resistance in glioblastoma patients. npj Genomic Medicine, 2023; 8 (1) DOI: 10.1038/s41525-023-00381-w

University of Notre Dame. (2023, December 12). Understudied cell in the brain could be key to treating glioblastoma. ScienceDaily. Retrieved December 12, 2023 from www.sciencedaily.com/releases/2023/12/231212112310.htm

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