Expression of Hv1 proton channels in myeloid-derived suppressor cells (MDSC) and its potential role in T cell regulation

Juan J. Alvear-Arias, Christian Carrillo, Javiera Paz Villar, Richard Garcia-Betancourt, Antonio Peña-Pichicoi, Audry Fernandez, Miguel Fernandez, Emerson M. Carmona, Amaury Pupo, Alan Neely, Osvaldo Alvarez, Jose Garate, Héctor Barajas-Martinez, H. Peter Larsson, Angélica Lopez-Rodriguez, Ramon Latorre, Carlos Gonzalez

Research output: Contribution to journalArticlepeer-review

Abstract

SignificanceImmunosuppression by myeloid-derived suppressor cells (MDSC), especially near tumor surfaces, involves the extracellular production of reactive oxygen species (ROS). ROS generation in MDSC occurs during the oxidation of NADPH to NADP+, which NOX2 catalyzes. ROS react with the T cell receptor complex, abolishing the antigen presentation, which blocks the immune system elimination of the tumor cells. Extrusion of protons from MDSC by voltage-gated proton channel (Hv1) sustains ROS production. Here, we demonstrate the expression of Hv1 in mouse MDSC. In this way, Hv1 present in MDSC becomes a potential cancer therapeutic target since its inhibition seems to diminish immunosuppression activity in the tumoral microenvironment, allowing cancer cells to be attacked by the immune system.

Original languageEnglish (US)
Pages (from-to)e2104453119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number15
DOIs
StatePublished - Apr 12 2022
Externally publishedYes

Keywords

  • Hv1 channel
  • NOX2 complex
  • ROS
  • immunosuppression
  • myeloid cells

ASJC Scopus subject areas

  • General

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