Glioblastoma (GBM), an aggressive form of cancer that grows in the brain or spinal cord, occurs at an incidence rate of about 3/100,000 persons in the United States. Effective treatments remain significantly lacking, and the fast-growing nature of GBM poses significant challenges to clinical research. Thus, ongoing research that helps oncologists understand how GBM forms, grows, and responds to treatment can provide valuable information on better disease control.
The tumor microenvironment (TME) describes the cells, molecules, blood vessels, and other mediators present near a tumor. All components within the TME can interact with tumor cells, and the contact can benefit or harm cancer. Cells and immune mediators that promote anti-cancer activity can work to fight the tumor, whereas other components within the TME can suppress anti-cancer activity and even fuel tumor growth. Thus, the balance of the mediators present in the TME can significantly impact outcomes.
Traditional therapies, including surgery, radiation, and chemotherapy rarely elicit durable responses in GBM, and the lack of infiltration of CD8 T cells into the GBM microenvironment makes these cancers non-responsive to immunotherapies. A recent study published in Science has identified a different subset of immune cells present in the GBM microenvironment that suppress anti-tumor immune responses against GBM.
The study focused on myeloid-derived suppressor cells (MDSCs), immune cells that prevent CD8 T cells from killing cancer cells, contributing to cancer growth and progression. The researchers used large-scale transcriptomic techniques to understand the precise role of MDSCs in GBM.
The study identified populations of MDSCs present in the most aggressive, advanced GBM tumors. These cells, defined as early-MSDCs (E-MDSCs) divided more rapidly than other MDSCs. In addition, E-MDSCs utilized cellular pathways associated with metabolism more frequently than other cells. Notably, metabolically active cells correlate with aggressive cancer subtypes.
The researchers uncovered another key characteristic of E-MDSCs when examining their interactions with GBM cells. The research demonstrated that tumor cells produced chemokines, proteins that elicit movement of immune cells within the body, which drew E-MDSC movement into the GBM microenvironment.
The authors conclude that GBM promotes their own growth by communicating with E-MDSC and promoting their accumulation in the TME. Once they arrive at specific regions of the GBM tumor, E-MDSCs produce immune mediators that further drive the rapid growth of tumors. This understanding of the role of E-MDSCs in GBM opens up new possibilities for research and potential therapeutic strategies, inspiring further exploration and innovation in the field of cancer biology and treatment.
Sources: Glioblastoma, Science, Cancer Immunol Res