P-selectin axis plays a key role in microglia immunophenotype and 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 demonstrate these findings by pharmacological and molecular inhibition of P-selectin which leads to reduced tumor growth and increased survival in GB mouse models. Our work sheds light on tumor-associated microglia/macrophage 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. Glioma-associated microglia/macrophages are central drivers of brain tumor pathology. Here the authors characterize the role of the P-selectin/PSGL-1 axis in the cross-talk between glioblastoma cells and microglia/macrophages and show that the therapeutic targeting of P-selectin limits glioblastoma progression in preclinical models.

Automated summary

The study revealed the crucial role of P-selectin in promoting GB proliferation and invasion, showing that inhibiting P-selectin could reduce tumor growth and increase survival in mouse models. The findings shed light on the function of tumor-associated microglia/macrophages 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.