Hv1 channel is a key target in immunosupression in myeloid-derived suppressor cells (MDSC)

CARRILLO, CHRISTIAN A.; ALVEAR ARIAS, JUAN JOSÉ; PEÑA-PICHICOI, ANTONIO; FERNANDEZ, MIGUEL; CARMONA, EMERSON M.; NEELY, ALAN; ALVAREZ, OSVALDO; GARATE, JOSE ANTONIO; LARSSON, H. PETE; LOPEZ-RODRIGUEZ, ANGELICA M.; LATORRE, RAMON; GONZALEZ, CARLOS

San Francisco, California

Congreso; 66th Biophysical Society Annual Meeting; 2022

Biophysical Society

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that has a high immunosuppressive activity and proliferates in infections, inflammation and tumor microenvironments. In tumors, MDSCs exert immunosuppression mainly by producing reactive oxygen species (ROS), a process triggered by the NADPH oxidase 2 (NOX2) activity. In certain immune cells, NOX2 is functionally coupled with the Hv1 channel to support the sustained free-radical production. However, a functional expression of the Hv1 channel in MDSCs has not been reported yet. Here, we demonstrate that mouse MDSCs express functional Hv1 channel by immunofluorescence microscopy, flow-cytometry, Western Blot, besides performing a biophysical characterization of its currents via patch-clamp technique. Our results show a decrease in the immunosuppression capabilities of MDSC when exposed to Hv1 inhibitors, which correlates with a reduction of their ROS production profile that appears when the proton channel is inhibited, even displaying a phenotypical shift among MDSCs. The immunosuppression by MDSCs is conditioned to their ability to decrease the proton concentration elevated by the NOX2 activity, rendering Hv1 as a potential drug target for cancer treatment.