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GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer
Accepting the crucial role of the immune microenvironment (TME) in tumor progression enables us to identify immunotherapeutic targets and develop new therapies. Glycoprotein A repetitions predominant (GARP) plays a vital part in maintaining regulatory T cell (Treg)-mediated immune tolerance. The imp...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378229/ https://www.ncbi.nlm.nih.gov/pubmed/34421887 http://dx.doi.org/10.3389/fimmu.2021.660397 |
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author | Jiang, Sutian Zhang, Yifan Zhang, Xiaojing Lu, Bing Sun, Pingping Wu, Qianqian Ding, Xuzhong Huang, Jianfei |
author_facet | Jiang, Sutian Zhang, Yifan Zhang, Xiaojing Lu, Bing Sun, Pingping Wu, Qianqian Ding, Xuzhong Huang, Jianfei |
author_sort | Jiang, Sutian |
collection | PubMed |
description | Accepting the crucial role of the immune microenvironment (TME) in tumor progression enables us to identify immunotherapeutic targets and develop new therapies. Glycoprotein A repetitions predominant (GARP) plays a vital part in maintaining regulatory T cell (Treg)-mediated immune tolerance. The impact of GARP in TME of gastric cancer is still worth exploring. We investigated public genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus to analyze the possible role of GARP and its relationship with TME of gastric cancer. Fluorescence-based multiplex immunohistochemistry and immunohistochemistry for T-cell immune signatures in a series of tissue microarrays were used to validate the value of GARP in the TME. We initially found that GARP expression was upregulated in gastric carcinoma cells, and diverse levels o3f immune cell infiltration and immune checkpoint expression were detected. Gene expression profiling revealed that GARP expression was related to the TME of gastric cancer. GARP upregulation was usually accompanied by increased FOXP3+ Treg and CD4+ T cell infiltration. In addition, GARP expression had positive relationships with CTLA-4 and PD-L1 expression in gastric cancer. Cox regression analysis and a nomogram highlighted that the probability of poor overall survival was predicted well by GARP or GARP+CD4+ T cell. Taken together, this research underlines the potential effect of GARP in regulating survival and tumor-infiltrating T-cells. In addition, the function of CD4+ T cell immune signatures in the prognosis can be clinically meaningful, thereby providing a new idea for the immunotherapeutic approach. |
format | Online Article Text |
id | pubmed-8378229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83782292021-08-21 GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer Jiang, Sutian Zhang, Yifan Zhang, Xiaojing Lu, Bing Sun, Pingping Wu, Qianqian Ding, Xuzhong Huang, Jianfei Front Immunol Immunology Accepting the crucial role of the immune microenvironment (TME) in tumor progression enables us to identify immunotherapeutic targets and develop new therapies. Glycoprotein A repetitions predominant (GARP) plays a vital part in maintaining regulatory T cell (Treg)-mediated immune tolerance. The impact of GARP in TME of gastric cancer is still worth exploring. We investigated public genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus to analyze the possible role of GARP and its relationship with TME of gastric cancer. Fluorescence-based multiplex immunohistochemistry and immunohistochemistry for T-cell immune signatures in a series of tissue microarrays were used to validate the value of GARP in the TME. We initially found that GARP expression was upregulated in gastric carcinoma cells, and diverse levels o3f immune cell infiltration and immune checkpoint expression were detected. Gene expression profiling revealed that GARP expression was related to the TME of gastric cancer. GARP upregulation was usually accompanied by increased FOXP3+ Treg and CD4+ T cell infiltration. In addition, GARP expression had positive relationships with CTLA-4 and PD-L1 expression in gastric cancer. Cox regression analysis and a nomogram highlighted that the probability of poor overall survival was predicted well by GARP or GARP+CD4+ T cell. Taken together, this research underlines the potential effect of GARP in regulating survival and tumor-infiltrating T-cells. In addition, the function of CD4+ T cell immune signatures in the prognosis can be clinically meaningful, thereby providing a new idea for the immunotherapeutic approach. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8378229/ /pubmed/34421887 http://dx.doi.org/10.3389/fimmu.2021.660397 Text en Copyright © 2021 Jiang, Zhang, Zhang, Lu, Sun, Wu, Ding and Huang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Jiang, Sutian Zhang, Yifan Zhang, Xiaojing Lu, Bing Sun, Pingping Wu, Qianqian Ding, Xuzhong Huang, Jianfei GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer |
title | GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer |
title_full | GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer |
title_fullStr | GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer |
title_full_unstemmed | GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer |
title_short | GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer |
title_sort | garp correlates with tumor-infiltrating t-cells and predicts the outcome of gastric cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378229/ https://www.ncbi.nlm.nih.gov/pubmed/34421887 http://dx.doi.org/10.3389/fimmu.2021.660397 |
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