TMIC-09. HV1 PROTON CHANNELS PROMOTE MYELOID INFILTRATION AND GLIOMA PROGRESSION

Abstract Myeloid cells comprising up to 50% of total tumor mass in glioblastoma (GBM) contribute progression and immunosuppression. Restraining glioma-induced myeloid cell infiltration increases functional T within the tumors, improves efficacy checkpoint blockade, significantly extends mouse survival. Here, we focus on an ion channel, voltage-gated proton channel Hv1, which is mainly expressed shapes physiological functions cells. Our bioinformatics analysis demonstrated that elevated Hv1 expression correlates with poor disease prognosis patients. Using leading immunocompetent model GBM mice, showed knockout mice (Hv1-/-) exhibit slower glioma prolonged Notably, vivo two-photon imaging, immunofluorescence, full-spectrum flow cytometry revealed Hv1-/- have reduced monocyte/macrophage infiltration, higher frequency MHCII+ among all infiltrating cells, increased PD-1+CD4+ tumor-burdened hemisphere. As a result, combined anti-PD-1 treatment middle stage glioma, found approximately 30% were cured. Together, our results regulates could be novel therapeutic target for GBM.