Expression of H<sub>v</sub>1 proton channels in myeloid-derived suppressor cells (MDSC) and its potential role in T cell regulation-Reference-Cited by-同舟云学术

Expression of H_v1 proton channels in myeloid-derived suppressor cells (MDSC) and its potential role in T cell regulation

Published:2022-04-04 Issue:15 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Alvear-Arias Juan J.¹²^ORCID,Carrillo Christian¹²^ORCID,Villar Javiera Paz¹^ORCID,Garcia-Betancourt Richard¹,Peña-Pichicoi Antonio¹²,Fernandez Audry¹,Fernandez Miguel¹²,Carmona Emerson M.¹^ORCID,Pupo Amaury¹,Neely Alan¹^ORCID,Alvarez Osvaldo¹³^ORCID,Garate Jose¹²^ORCID,Barajas-Martinez Héctor⁴^ORCID,Larsson H. Peter⁵^ORCID,Lopez-Rodriguez Angélica⁶^ORCID,Latorre Ramon¹^ORCID,Gonzalez Carlos¹²³

Affiliation:

1. Millenium Institute Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 236 0102, Chile

2. Millenium Nucleus in NanoBioPhysics (NNBP), Universidad de Valparaíso, Valparaíso 236 0102, Chile

3. Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Santiago 7800003, Chile

4. Cardiovascular Research, Lankenau Institute for Medical Research, Wynnewood, PA 19096

5. Department of Physiology & Biophysics, University of Miami, Coral Gables, FL 33101

6. Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Durango 34000, México

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.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2104453119

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