Research Snapshot: UF study provides insight into the role of myeloid cells in glioma progression

By Ian Bennett

Research from the University of Florida Health Cancer Center sheds light on the complex interactions between cancer cells and the immune system.

Gregory Takacs

Glioblastoma is a highly malignant form of brain cancer with a median survival rate for adults of 14.6 months. One of the critical challenges to treating this cancer is a tumor microenvironment (TME), which suppresses the body’s anti-tumor immune system from entering and attacking the cancer.

The study, published in Frontiers in Immunology, focused on a subset of monocytic-myeloid-derived suppressor cells (M-MDSCs) expressing two chemokine receptors, CCR2 and CX3CR1. The data collected in this study provides the clearest picture to date on how these two receptors allow certain cells to enter the TME. It also provides a better understanding of the role of CCL2 and CCL7, which are chemoattractant cytokines. These proteins bind to the receptors studied in this project and help carry immune suppressive cells into the TME. 

Gregory Takacs, a Ph.D. candidate in the biomedical sciences program at the University Florida with a cancer biology concentration, led the study under the guidance of mentor Jeffrey K. Harrison, Ph.D., a professor in the department of pharmacology and therapeutics in the UF College of Medicine. Through the project, they built upon previous CCR2+/CX3CR1+ myeloid cell research.

“Previous work from our lab established that these CCR2+/CX3CR1+ myeloid cells share markers of myeloid-derived suppressor cells and utilize the chemokine receptor CCR2 to gain access into the glioma,” said Takacs. “The goal of this study was to further examine this cell population to first identify their origin, second to functionally test their immune suppressive capabilities and third to elucidate the important chemokines that are mediating MDSC migration into the glioma.”

To do this, they investigated the T-cell suppressive function and chemokine-ligand dependency, which were thought to be used by CCR2+/CX3CR1+ M-MDSCs to traffic into the glioma microenvironment. Using a preclinical glioma model, the team demonstrated that CCR2+/CX3CR1+ cells are sourced from the bone marrow. They also showed that these cells suppress both CD4+ and CD8+ T cells. They also established that the cells migrate to CCL2 and/or CCL7 chemokines, are mediated through the CCR2 receptor, and are reduced in the glioma microenvironment through combination targeting of CCL2 and CCL7. The team also identified CCL2 and CCL7 as predictors of survival in human glioblastoma. Lower levels of these two chemokines were associated with better outcomes in glioblastoma patients.

This research demonstrates the need for continued research into the interactions between the immune system and brain cancer cells. By establishing the immune-suppressive and migratory properties of CCR2+/CX3CR1+ myeloid cells, Takacs, Harrison and their collaborators hope that these findings will lead to more detailed research and new treatments to improve the prognosis for patients with glioma.

Read the study in Frontiers in Immunology.

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