Cell in Brain Critical for Glioblastoma Treatment

Glioblastoma, a highly resistant cancer, often results in survival periods of under two years after diagnosis. In a recent NPJ Genomic Medicine study, scientists from the University of Notre Dame discovered that a relatively overlooked cell might provide fresh understanding regarding how this aggressive form of brain cancer eludes immunotherapy.

According to Meenal Datta, an assistant professor of aerospace and mechanical engineering at Notre Dame and the study’s senior author, the existence of perivascular fibroblasts within the brain, not just the skull lining, was unknown a decade ago.

Cell in brain critical for glioblastoma treatment: examining tumors

“My laboratory specializes in examining tumors through an engineering and system-oriented approach, focusing on unique mechanical attributes present in rare, underexplored cancers.”

Employing both traditional bioinformatics and cutting-edge AI techniques, Datta’s TIME Lab initiated an investigation into the diverse genes expressed within the tumor microenvironment, particularly those linked to the extracellular matrix. This matrix acts as a scaffold facilitating cell adhesion, migration, proliferation, and differentiation, among other functions.

Their exploration led to an unexpected discovery: the identification of a relatively new cell type known as perivascular fibroblasts. Normally found in healthy brain blood vessels, these fibroblasts play a role in depositing collagen to maintain the structural integrity and functionality of brain vessels.

So, Maksym Zarodniuk, a graduate student in the TIME Lab and the bioengineering doctorate program, and the primary author of the study, referred to this revelation as a fortuitous find. Their investigation, initially aimed in a different direction, stumbled upon this cell population by combining bulk and single-cell RNA sequencing analyses of patient tumors.

Cell in brain critical for glioblastoma treatment: perivascular fibroblasts

Analyzing their data, researchers categorized patients into two groups based on the prevalence of perivascular fibroblasts within their tumors. The study found that patients with a higher proportion of these fibroblasts responded less favorably to immunotherapies and exhibited poorer survival rates.

Further exploration uncovered that perivascular fibroblasts play a crucial role in establishing an immunosuppressive environment within the tumor, aiding the cancer’s evasion of the immune system. Additionally, these fibroblasts potentially contribute to the cancer’s resistance to therapies, such as chemotherapy, by promoting stem-like cancer cells that exhibit low division rates, known as a key factor in tumor relapse and spread.

“Moving ahead, our aim is to conduct further experiments to validate our findings from this paper and establish a foundation for enhancing responses to immunotherapy,” Zarodniuk commented.

The brain’s healthy vasculature

Datta suggests that perivascular fibroblasts, a part of the brain’s healthy vasculature, may be migrating or infiltrating glioblastoma tumors. However, instead of supporting normal brain function, these fibroblasts undergo reprogramming, aiding the tumor’s growth.

Most people perceive the brain as soft, comprising soft cells and a pliable matrix. Datta highlighted how fibroblasts and fibrous proteins provide new insights into how cancer cells exploit the brain’s structure.

Therefore, the study involved collaborations with Notre Dame researchers, including Jun Li, who developed deep learning algorithms, and Xin Lu, a Biological Sciences professor.

Datta is linked to numerous Notre Dame institutes, including the Berthiaume Institute for Precision Health, Eck Institute for Global Health, Harper Cancer Research Institute, Lucy Family Institute for Data and Society, NDnano, and Warren Center for Drug Discovery.

Datta, as an assistant professor, participates in multiple doctoral programs in engineering and bioengineering.

This research received funding from the National Cancer Institute.

Read the original article on sciencedaily

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