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Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment

The glioma tumor microenvironment (TME), composed of several noncancerous cells and biomolecules is known for its complexity of cancer-immune system interaction. Given that, novel risk signature is required for predicting glioma patient responses to immunotherapy. In this study, we systematically ev...

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Autores principales: Zhang, Nan, Zhang, Hao, Wang, Zeyu, Dai, Ziyu, Zhang, Xun, Cheng, Quan, Liu, Zhixiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418124/
https://www.ncbi.nlm.nih.gov/pubmed/34489938
http://dx.doi.org/10.3389/fimmu.2021.691811
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author Zhang, Nan
Zhang, Hao
Wang, Zeyu
Dai, Ziyu
Zhang, Xun
Cheng, Quan
Liu, Zhixiong
author_facet Zhang, Nan
Zhang, Hao
Wang, Zeyu
Dai, Ziyu
Zhang, Xun
Cheng, Quan
Liu, Zhixiong
author_sort Zhang, Nan
collection PubMed
description The glioma tumor microenvironment (TME), composed of several noncancerous cells and biomolecules is known for its complexity of cancer-immune system interaction. Given that, novel risk signature is required for predicting glioma patient responses to immunotherapy. In this study, we systematically evaluated the TME infiltration pattern of 2877 glioma samples. TME phenotypes were determined using the Partitioning Around Medoid method. Machine learning including SVM-RFE and Principal component analysis (PCA) were used to construct a TME scoring system. A total of 857 glioma samples from four datasets were used for external validation of the TME-score. The correlation of TME phenotypes and TME-scores with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in glioma patients was determined. Immunohistochemistry staining for the M2 macrophage marker CD68 and CD163, mast cell marker CD117, neutrophil marker CD66b, and RNA sequencing of glioma samples from the XYNS cohort were performed. Two distinct TME phenotypes were identified. High TME-score correlated with a high number of immune infiltrating cells, elevated expression of immune checkpoints, increased mutation rates of oncogenes, and poor survival of glioma patients. Moreover, high TME-score exhibited remarkable association with multiple immunomodulators that could potentially mediate immune escape of cancer. Thus, the TME-score showed the potential to predict the efficacy of anti-PD-1 immunotherapy. Univariate and multivariate analyses demonstrated the TME-score to be a valuable prognostic biomarker for gliomas. Our study demonstrated that TME could potentially influence immunotherapy efficacy in melanoma patients whereas its role in immunotherapy of glioma patients remains unknown. Therefore, a better understanding of the TME landscape in gliomas would promote the development of novel immunotherapy strategies against glioma.
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spelling pubmed-84181242021-09-05 Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment Zhang, Nan Zhang, Hao Wang, Zeyu Dai, Ziyu Zhang, Xun Cheng, Quan Liu, Zhixiong Front Immunol Immunology The glioma tumor microenvironment (TME), composed of several noncancerous cells and biomolecules is known for its complexity of cancer-immune system interaction. Given that, novel risk signature is required for predicting glioma patient responses to immunotherapy. In this study, we systematically evaluated the TME infiltration pattern of 2877 glioma samples. TME phenotypes were determined using the Partitioning Around Medoid method. Machine learning including SVM-RFE and Principal component analysis (PCA) were used to construct a TME scoring system. A total of 857 glioma samples from four datasets were used for external validation of the TME-score. The correlation of TME phenotypes and TME-scores with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in glioma patients was determined. Immunohistochemistry staining for the M2 macrophage marker CD68 and CD163, mast cell marker CD117, neutrophil marker CD66b, and RNA sequencing of glioma samples from the XYNS cohort were performed. Two distinct TME phenotypes were identified. High TME-score correlated with a high number of immune infiltrating cells, elevated expression of immune checkpoints, increased mutation rates of oncogenes, and poor survival of glioma patients. Moreover, high TME-score exhibited remarkable association with multiple immunomodulators that could potentially mediate immune escape of cancer. Thus, the TME-score showed the potential to predict the efficacy of anti-PD-1 immunotherapy. Univariate and multivariate analyses demonstrated the TME-score to be a valuable prognostic biomarker for gliomas. Our study demonstrated that TME could potentially influence immunotherapy efficacy in melanoma patients whereas its role in immunotherapy of glioma patients remains unknown. Therefore, a better understanding of the TME landscape in gliomas would promote the development of novel immunotherapy strategies against glioma. Frontiers Media S.A. 2021-08-13 /pmc/articles/PMC8418124/ /pubmed/34489938 http://dx.doi.org/10.3389/fimmu.2021.691811 Text en Copyright © 2021 Zhang, Zhang, Wang, Dai, Zhang, Cheng and Liu 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
Zhang, Nan
Zhang, Hao
Wang, Zeyu
Dai, Ziyu
Zhang, Xun
Cheng, Quan
Liu, Zhixiong
Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment
title Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment
title_full Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment
title_fullStr Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment
title_full_unstemmed Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment
title_short Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment
title_sort immune infiltrating cells-derived risk signature based on large-scale analysis defines immune landscape and predicts immunotherapy responses in glioma tumor microenvironment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418124/
https://www.ncbi.nlm.nih.gov/pubmed/34489938
http://dx.doi.org/10.3389/fimmu.2021.691811
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