Characterizing the immunosuppressive role of myeloid-derived suppressor cells in glioblastoma under radiotherapy

In this work, we address the treatment of glioblastoma (GBM), a difficult-to-treat brain cancer. Upon discovery of GBM, patients are frequently treated with both surgery and chemoradiotherapy but still suffer from eventual recurrence due to unresectable microscopic disease that evades adjuvant therapy. The disease is characterized by an immunosuppressive tumor microenvironment. Immunotherapies, including immune checkpoint inhibitors, have been trialed in GBM but have so far failed to improve otherwise bleak outcomes for GBM patients. One possible way GBM tumors sustain this immune suppression, even in the face of ICI, is through recruitment and sustaining a population of myeloid-derived suppressor cells (MDSCs). These potently immunosuppressive cells decrease T-cell activity through a range of mechanisms including direct cell-cell interactions, secretion of T-cell inhibitors, and alteration of the metabolic environment. Furthermore, radiotherapy (RT), which can paradoxically lead to both immunosuppression and immune stimulation, represents an underexplored option to possibly tip the tumor in favor of immune stimulation. To understand the interplay between MDSCs, effector cells, and RT, we developed a dynamic, computational model of the tumor immune microenvironment of glioblastoma.

Characterizing the immunosuppressive role of myeloid-derived suppressor cells in glioblastoma under radiotherapy

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Xuanming Zhang

"Characterizing the immunosuppressive role of myeloid-derived suppressor cells in glioblastoma under radiotherapy"

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