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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...

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Autores principales: Jiang, Sutian, Zhang, Yifan, Zhang, Xiaojing, Lu, Bing, Sun, Pingping, Wu, Qianqian, Ding, Xuzhong, Huang, Jianfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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