By Viva Voong ‘26
Edited by Evan MacLure ‘26
Glioblastoma is one of the most aggressive types of cancers, with a median survival rate of 15 months. [1] Many researchers have been working to develop treatments to target brain tumors and potentially cure glioblastoma. However, these attempts have met little success and clinical trials have shown limited clinical benefits, due to the aggressiveness of brain tumors, but more importantly, the heterogeneity of the tumor microenvironment. Proteins, signaling pathways, mutations and different cellular states create diverse conditions that can be difficult to treat. [2]
Figure 1. Components of GBM Tumor Microenvironment. Image Credit: Dapash et al.
Working to understand the diverse components of the tumor microenvironment may allow researchers to develop more effective treatments for brain tumors. As shown in Figure 1, glioblastoma tumor microenvironment consists of macrophages, dendritic cells, myeloid-derived suppressor cells, neutrophils, B lymphocytes, T lymphocytes, natural killer cells and glioblastoma cells among many others. These components have biological roles that contribute to the resistance of the GBM tumor. For example, myeloid cells promote differentiation of regulatory B and T cells. In addition, natural killer cells enhance glioma stem cell resistance to cytotoxicity. Finally, T lymphocytes express proteins that suppress the anti tumor response. [3]
Wider components of the tumor microenvironment, such as the extracellular matrix, blood brain barrier and central nervous system can also influence the resistance of the tumor to various treatments. Cellular components interact with the extracellular matrix to strengthen mobility and invasiveness. The blood-brain barrier is compromised in the GBM microenvironment due to inflammation, changes in form and increased leakiness of blood vessels. [3]
In addition, signaling pathways such as the PI3K/AKT/mTOR pathway plays an important role in cell growth, proliferation and metabolism, which can affect the tumor and microenvironment. Interruptions to this pathway can alter tumor growth and resistance. [3]
While developing treatments, researchers must consider the effects of the tumor microenvironment as these interactions heavily affect the versatility of the tumor. Researchers are currently working to combine treatments to more effectively treat tumors. They are also looking into timing of treatment administration to produce the most effective results. In addition, scientists are hoping to develop a vaccine that can combat tumor cells. [2]
Glioblastoma remains an exciting area of research with potential for new treatments and fascinating discoveries. Fully understanding GBM and how their physiological components and pathways contribute to the tumor microenvironment can provide key insight into producing novel cancer vaccines and treatments.
Sources:
Kanderi T, Gupta V. Glioblastoma Multiforme [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 9]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558954/#:~:text=Glioblastoma%20multiforme%20%28GBM%29%20is%20the%20most%20common%20primary
Pombo Antunes AR, Scheyltjens I, Duerinck J, Neyns B, Movahedi K, Van Ginderachter JA. Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies. eLife [Internet]. [cited 2020 Nov 6];9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000215/
Dapash M, Hou D, Castro B, Lee-Chang C, Lesniak MS. The Interplay between Glioblastoma and Its Microenvironment. Cells. 2021 Aug 31;10(9):2257.
Johns Hopkins Medicine. A Potential New Target to Fight Glioblastoma [image on the Internet]. [Date unknown] [cited 2023 Aug 25]. Available from: https://clinicalconnection.hopkinsmedicine.org/news/a-potential-new-target-to-fight-glioblastoma
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