Researchers Look for Novel Immunomodulating Target
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Glioblastoma remains one of the most debilitating and difficult-to-treat types of brain cancer. This type of cancer originates from the supportive tissue of nerve cells in the brain and spinal cord before very quickly invading and damaging healthy brain tissue. The speed with which glioblastomas proliferate, their proximity to crucial brain tissue and their potent immune-suppression abilities make treating glioblastomas incredibly difficult and often result in low survival outcomes for patients once they are diagnosed.
With a five-year survival rate of only 6.9% and an average postdiagnosis survival rate of around eight months, glioblastoma takes more than 100,000 lives in the United States every year.
Researchers are now studying the spatial, molecular and cellular heterogeneity of glioblastoma cells to find potential targets for immunotherapy treatment and improve the effectiveness of glioblastoma treatments. Published in the journal “EMBO Molecular Medicine,” the study sought to expand immunotherapy treatments for glioblastoma and make them more effective by searching for novel immunomodulating targets.
Glioblastoma currently has an average survival rate of only two years after diagnosis as the immunosuppressive microenvironment created by glioblastoma tumors coupled with their heterogeneity makes this type of brain cancer incredibly resistant to conventional treatments. Unlike other macrophages, glioblastomas comprise “highly plastic immune cells” with potent immunosuppressive properties that severely limit the immune system’s ability to identify and kill cancer cells and reduce the overall effectiveness of immunotherapies.
Researchers performed several experiments on GBM stem cell cultures (GSCCs) extracted from glioblastoma patients and blended with GBM-associated macrophage (GAM)-GBM co-cultures. This included scRNA-seq (single-cell ribonucleic acid sequencing) of seven GSCC sets as well as real-time in vivo monitoring of GAM-BBM interactions in models of orthotopic zebrafish xenografts.
The research team collected up to 5,320 cells from GAM monoculture and eight co-cultures with an average number of 3,334 genes per cell. Analysis revealed GAM heterogeneity at a molecular level, a phenotype switch in vivo and in vitro, and cell-cell interaction patterns that were specific to different patients. According to the team’s findings, the LGALS1 gene played a primary role in immunosuppression in glioblastoma tumors. Consequently, the team posited that changes in the expression of the LGALS1 gene may have an impact on glioblastoma survival rates.
This research adds to prior studies, which found that LGALS1 can increase patient resistance to both immunotherapy and chemotherapy. It potentially opens the door to immunotherapies and drugs that target the LGALS1 gene to improve treatment outcomes for glioblastoma.
As more scientists search for ways to make immunotherapy work better for patients with glioblastoma, efforts are also ongoing by companies such as CNS Pharmaceuticals Inc. (NASDAQ: CNSP) to develop novel drugs that can offer glioblastoma patients better clinical outcomes.
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