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The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy

Gliomas are a type of malignant central nervous system tumor with poor prognosis. Molecular biomarkers of gliomas can predict glioma patient’s clinical outcome, but their limitations are also emerging. C-X-C motif chemokine ligand family plays a critical role in shaping tumor immune landscape and mo...

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Autores principales: Wang, Zeyu, Liu, Yuze, Mo, Yuyao, Zhang, Hao, Dai, Ziyu, Zhang, Xun, Ye, Weijie, Cao, Hui, Liu, Zhixiong, Cheng, Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482424/
https://www.ncbi.nlm.nih.gov/pubmed/34603309
http://dx.doi.org/10.3389/fimmu.2021.731751
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author Wang, Zeyu
Liu, Yuze
Mo, Yuyao
Zhang, Hao
Dai, Ziyu
Zhang, Xun
Ye, Weijie
Cao, Hui
Liu, Zhixiong
Cheng, Quan
author_facet Wang, Zeyu
Liu, Yuze
Mo, Yuyao
Zhang, Hao
Dai, Ziyu
Zhang, Xun
Ye, Weijie
Cao, Hui
Liu, Zhixiong
Cheng, Quan
author_sort Wang, Zeyu
collection PubMed
description Gliomas are a type of malignant central nervous system tumor with poor prognosis. Molecular biomarkers of gliomas can predict glioma patient’s clinical outcome, but their limitations are also emerging. C-X-C motif chemokine ligand family plays a critical role in shaping tumor immune landscape and modulating tumor progression, but its role in gliomas is elusive. In this work, samples of TCGA were treated as the training cohort, and as for validation cohort, two CGGA datasets, four datasets from GEO database, and our own clinical samples were enrolled. Consensus clustering analysis was first introduced to classify samples based on CXCL expression profile, and the support vector machine was applied to construct the cluster model in validation cohort based on training cohort. Next, the elastic net analysis was applied to calculate the risk score of each sample based on CXCL expression. High-risk samples associated with more malignant clinical features, worse survival outcome, and more complicated immune landscape than low-risk samples. Besides, higher immune checkpoint gene expression was also noticed in high-risk samples, suggesting CXCL may participate in tumor evasion from immune surveillance. Notably, high-risk samples also manifested higher chemotherapy resistance than low-risk samples. Therefore, we predicted potential compounds that target high-risk samples. Two novel drugs, LCL-161 and ADZ5582, were firstly identified as gliomas’ potential compounds, and five compounds from PubChem database were filtered out. Taken together, we constructed a prognostic model based on CXCL expression, and predicted that CXCL may affect tumor progression by modulating tumor immune landscape and tumor immune escape. Novel potential compounds were also proposed, which may improve malignant glioma prognosis.
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spelling pubmed-84824242021-10-01 The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy Wang, Zeyu Liu, Yuze Mo, Yuyao Zhang, Hao Dai, Ziyu Zhang, Xun Ye, Weijie Cao, Hui Liu, Zhixiong Cheng, Quan Front Immunol Immunology Gliomas are a type of malignant central nervous system tumor with poor prognosis. Molecular biomarkers of gliomas can predict glioma patient’s clinical outcome, but their limitations are also emerging. C-X-C motif chemokine ligand family plays a critical role in shaping tumor immune landscape and modulating tumor progression, but its role in gliomas is elusive. In this work, samples of TCGA were treated as the training cohort, and as for validation cohort, two CGGA datasets, four datasets from GEO database, and our own clinical samples were enrolled. Consensus clustering analysis was first introduced to classify samples based on CXCL expression profile, and the support vector machine was applied to construct the cluster model in validation cohort based on training cohort. Next, the elastic net analysis was applied to calculate the risk score of each sample based on CXCL expression. High-risk samples associated with more malignant clinical features, worse survival outcome, and more complicated immune landscape than low-risk samples. Besides, higher immune checkpoint gene expression was also noticed in high-risk samples, suggesting CXCL may participate in tumor evasion from immune surveillance. Notably, high-risk samples also manifested higher chemotherapy resistance than low-risk samples. Therefore, we predicted potential compounds that target high-risk samples. Two novel drugs, LCL-161 and ADZ5582, were firstly identified as gliomas’ potential compounds, and five compounds from PubChem database were filtered out. Taken together, we constructed a prognostic model based on CXCL expression, and predicted that CXCL may affect tumor progression by modulating tumor immune landscape and tumor immune escape. Novel potential compounds were also proposed, which may improve malignant glioma prognosis. Frontiers Media S.A. 2021-09-13 /pmc/articles/PMC8482424/ /pubmed/34603309 http://dx.doi.org/10.3389/fimmu.2021.731751 Text en Copyright © 2021 Wang, Liu, Mo, Zhang, Dai, Zhang, Ye, Cao, Liu and Cheng 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
Wang, Zeyu
Liu, Yuze
Mo, Yuyao
Zhang, Hao
Dai, Ziyu
Zhang, Xun
Ye, Weijie
Cao, Hui
Liu, Zhixiong
Cheng, Quan
The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
title The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
title_full The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
title_fullStr The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
title_full_unstemmed The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
title_short The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy
title_sort cxcl family contributes to immunosuppressive microenvironment in gliomas and assists in gliomas chemotherapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482424/
https://www.ncbi.nlm.nih.gov/pubmed/34603309
http://dx.doi.org/10.3389/fimmu.2021.731751
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