Cargando…
CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment
PURPOSE: CTLA4, the immune checkpoint, has been widely reported to contribute to immune evasion in anti-tumor activity. The inhibitors of CTLA4 provide a novel strategy to improve the outcome of peripheral cancer, but their clinical effects are limited in glioblastoma (GBM), thus the comprehensive r...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712744/ https://www.ncbi.nlm.nih.gov/pubmed/34992419 http://dx.doi.org/10.2147/JIR.S341981 |
_version_ | 1784623621549850624 |
---|---|
author | Guan, Xiudong Wang, Yangyang Sun, Yueqian Zhang, Chuanbao Ma, Shunchang Zhang, Dainan Li, Deling Jia, Wang |
author_facet | Guan, Xiudong Wang, Yangyang Sun, Yueqian Zhang, Chuanbao Ma, Shunchang Zhang, Dainan Li, Deling Jia, Wang |
author_sort | Guan, Xiudong |
collection | PubMed |
description | PURPOSE: CTLA4, the immune checkpoint, has been widely reported to contribute to immune evasion in anti-tumor activity. The inhibitors of CTLA4 provide a novel strategy to improve the outcome of peripheral cancer, but their clinical effects are limited in glioblastoma (GBM), thus the comprehensive role of CTLA4 needs to be addressed. PATIENTS AND METHODS: A total of 471 GBM cases were enrolled in this study from 5 cohorts. In our works, the Cancer Genome Atlas (TCGA) cohort was divided into the training set, and the Chinese Glioma Genome Atlas (CGGA), REMBRANDT, and GSE84465 cohorts were divided into validation sets. Tissues from our cohort were collected for histopathologic validation. Then, the role of CTLA4 in the TME of GBM was comprehensively investigated. RESULTS: Significant differences exist in immunological characteristics between the low and high CTLA4 expression groups. Mutation analysis found different genomic patterns associated with CTLA4 expression. Next, network analysis found the module named c1-1562 including CTLA4 correlated with over survival (OS) in GBM. We also developed a predictive model to calculate the risk score for every GBM case and the risk score was independently related to OS. Furthermore, the expression of CTLA4 was positively related to the infiltration level and function of macrophage in GBM TME based on seven independent algorithms, single-cell RNA-seq data and immunohistochemistry. CONCLUSION: These findings implicate that CTLA4 could serve as a novel target for prognosis and therapy in GBM patients. CTLA4-mediated immune suppression may be attributed to the infiltration of macrophages in the tumor microenvironment. |
format | Online Article Text |
id | pubmed-8712744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-87127442022-01-05 CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment Guan, Xiudong Wang, Yangyang Sun, Yueqian Zhang, Chuanbao Ma, Shunchang Zhang, Dainan Li, Deling Jia, Wang J Inflamm Res Original Research PURPOSE: CTLA4, the immune checkpoint, has been widely reported to contribute to immune evasion in anti-tumor activity. The inhibitors of CTLA4 provide a novel strategy to improve the outcome of peripheral cancer, but their clinical effects are limited in glioblastoma (GBM), thus the comprehensive role of CTLA4 needs to be addressed. PATIENTS AND METHODS: A total of 471 GBM cases were enrolled in this study from 5 cohorts. In our works, the Cancer Genome Atlas (TCGA) cohort was divided into the training set, and the Chinese Glioma Genome Atlas (CGGA), REMBRANDT, and GSE84465 cohorts were divided into validation sets. Tissues from our cohort were collected for histopathologic validation. Then, the role of CTLA4 in the TME of GBM was comprehensively investigated. RESULTS: Significant differences exist in immunological characteristics between the low and high CTLA4 expression groups. Mutation analysis found different genomic patterns associated with CTLA4 expression. Next, network analysis found the module named c1-1562 including CTLA4 correlated with over survival (OS) in GBM. We also developed a predictive model to calculate the risk score for every GBM case and the risk score was independently related to OS. Furthermore, the expression of CTLA4 was positively related to the infiltration level and function of macrophage in GBM TME based on seven independent algorithms, single-cell RNA-seq data and immunohistochemistry. CONCLUSION: These findings implicate that CTLA4 could serve as a novel target for prognosis and therapy in GBM patients. CTLA4-mediated immune suppression may be attributed to the infiltration of macrophages in the tumor microenvironment. Dove 2021-12-23 /pmc/articles/PMC8712744/ /pubmed/34992419 http://dx.doi.org/10.2147/JIR.S341981 Text en © 2021 Guan et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Guan, Xiudong Wang, Yangyang Sun, Yueqian Zhang, Chuanbao Ma, Shunchang Zhang, Dainan Li, Deling Jia, Wang CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment |
title | CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment |
title_full | CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment |
title_fullStr | CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment |
title_full_unstemmed | CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment |
title_short | CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment |
title_sort | ctla4-mediated immunosuppression in glioblastoma is associated with the infiltration of macrophages in the tumor microenvironment |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712744/ https://www.ncbi.nlm.nih.gov/pubmed/34992419 http://dx.doi.org/10.2147/JIR.S341981 |
work_keys_str_mv | AT guanxiudong ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment AT wangyangyang ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment AT sunyueqian ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment AT zhangchuanbao ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment AT mashunchang ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment AT zhangdainan ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment AT lideling ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment AT jiawang ctla4mediatedimmunosuppressioninglioblastomaisassociatedwiththeinfiltrationofmacrophagesinthetumormicroenvironment |