The Voltage-Gated Hv1 H<sup>+</sup> Channel Is Expressed in Tumor-Infiltrating Myeloid-Derived Suppressor Cells
Myeloid-derived suppressor cells (MDSCs) are key determinants of the immunosuppressive microenvironment in tumors. As ion channels play key roles in the physiology/pathophysiology of immune cells, we aimed at studying the ion channel repertoire in tumor-derived polymorphonuclear (PMN-MDSC) and monoc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6216 |
| Summary: | Myeloid-derived suppressor cells (MDSCs) are key determinants of the immunosuppressive microenvironment in tumors. As ion channels play key roles in the physiology/pathophysiology of immune cells, we aimed at studying the ion channel repertoire in tumor-derived polymorphonuclear (PMN-MDSC) and monocytic (Mo-MDSC) MDSCs. Subcutaneous tumors in mice were induced by the Lewis lung carcinoma cell line (LLC). The presence of PMN-MDSC (CD11b<sup>+</sup>/Ly6G<sup>+</sup>) and Mo-MDSCs (CD11b<sup>+</sup>/Ly6C<sup>+</sup>) in the tumor tissue was confirmed using immunofluorescence microscopy and cells were identified as CD11b<sup>+</sup>/Ly6G<sup>+</sup> PMN-MDSCs and CD11b<sup>+</sup>/Ly6C<sup>+</sup>/F4/80<sup>−</sup>/MHCII<sup>−</sup> Mo-MDSCs using flow cytometry and sorting. The majority of the myeloid cells infiltrating the LLC tumors were PMN-MDSC (~60%) as compared to ~10% being Mo-MDSCs. We showed that PMN- and Mo-MDSCs express the Hv1 H<sup>+</sup> channel both at the mRNA and at the protein level and that the biophysical and pharmacological properties of the whole-cell currents recapitulate the hallmarks of Hv1 currents: ~40 mV shift in the activation threshold of the current per unit change in the extracellular pH, high H<sup>+</sup> selectivity, and sensitivity to the Hv1 inhibitor ClGBI. As MDSCs exert immunosuppression mainly by producing reactive oxygen species which is coupled to Hv1-mediated H<sup>+</sup> currents, Hv1 might be an attractive target for inhibition of MDSCs in tumors. |
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| ISSN: | 1661-6596 1422-0067 |