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Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)

Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expresse...

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Autores principales: Nam, Sorim, Lee, Aram, Lim, Jihyun, Lim, Jong-Seok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Applied Pharmacology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319546/
https://www.ncbi.nlm.nih.gov/pubmed/30521746
http://dx.doi.org/10.4062/biomolther.2018.201
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author Nam, Sorim
Lee, Aram
Lim, Jihyun
Lim, Jong-Seok
author_facet Nam, Sorim
Lee, Aram
Lim, Jihyun
Lim, Jong-Seok
author_sort Nam, Sorim
collection PubMed
description Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate NF-κB signaling. Moreover, expression of PD-L1 and CD80 on PD-1(+) MDSCs was higher than on PD-1(−) MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in PD-1(+) MDSCs than in PD-1(−) MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that PD-1(+) MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.
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spelling pubmed-63195462019-01-17 Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs) Nam, Sorim Lee, Aram Lim, Jihyun Lim, Jong-Seok Biomol Ther (Seoul) Original Article Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate NF-κB signaling. Moreover, expression of PD-L1 and CD80 on PD-1(+) MDSCs was higher than on PD-1(−) MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in PD-1(+) MDSCs than in PD-1(−) MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that PD-1(+) MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules. The Korean Society of Applied Pharmacology 2019-01 2018-12-06 /pmc/articles/PMC6319546/ /pubmed/30521746 http://dx.doi.org/10.4062/biomolther.2018.201 Text en Copyright ©2019, The Korean Society of Applied Pharmacology http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Nam, Sorim
Lee, Aram
Lim, Jihyun
Lim, Jong-Seok
Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)
title Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)
title_full Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)
title_fullStr Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)
title_full_unstemmed Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)
title_short Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)
title_sort analysis of the expression and regulation of pd-1 protein on the surface of myeloid-derived suppressor cells (mdscs)
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319546/
https://www.ncbi.nlm.nih.gov/pubmed/30521746
http://dx.doi.org/10.4062/biomolther.2018.201
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