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P-selectin Inhibition Alters Microglia Immunophenotype and Blocks Glioblastoma Progression

Glioblastoma (GB) is a highly invasive type of brain cancer exhibiting poor prognosis. As such, its microenvironment plays a crucial role in its progression. Among the brain stromal cells, the microglia were shown to facilitate GB invasion and immunosuppression. However, the reciprocal mechanisms by which GB cells alter microglia/macrophages behavior are not fully understood. We propose that these mechanisms involve adhesion molecules such as the Selectins family. These proteins are involved in immune modulation and cancer
immunity. We show that P-selectin mediates microglia-enhanced GB proliferation and
invasion by altering microglia/macrophages activation state. We validated these findings using pharmacological and molecular P-selectin inhibitors which led to reduced tumor growth and increased survival in GB mouse models. Our work sheds light on tumor-associated microglia/macrophages function and the mechanisms by which GB cells suppress the immune system and invade the brain, paving the way to exploit P-selectin as a target for GB therapy.