Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune Microenvironment
BackgroundThe glioma-associated stromal cell (GASC) is a recently identified type of cell in the glioma microenvironment and may be a prognostic marker for glioma. However, the potential mechanisms of GASCs in the glioma microenvironment remain largely unknown. In this work, we aimed to explore the...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-04-01
|
Series: | Frontiers in Oncology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.672928/full |
id |
doaj-da23797c8bba4bc299ecb5ec234abf5d |
---|---|
record_format |
Article |
spelling |
doaj-da23797c8bba4bc299ecb5ec234abf5d2021-04-29T10:44:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.672928672928Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune MicroenvironmentXiangming Cai0Feng Yuan1Feng Yuan2Junhao Zhu3Jin Yang4Chao Tang5Zixiang Cong6Zixiang Cong7Chiyuan Ma8Chiyuan Ma9Chiyuan Ma10Chiyuan Ma11School of Medicine, Southeast University, Nanjing, ChinaSchool of Medicine, Nanjing University, Nanjing, ChinaDepartment of Neurosurgery, Jinling Hospital, Nanjing, ChinaSchool of Medicine, Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, Jinling Hospital, Nanjing, ChinaDepartment of Neurosurgery, Jinling Hospital, Nanjing, ChinaSchool of Medicine, Nanjing University, Nanjing, ChinaDepartment of Neurosurgery, Jinling Hospital, Nanjing, ChinaSchool of Medicine, Southeast University, Nanjing, ChinaSchool of Medicine, Nanjing University, Nanjing, ChinaDepartment of Neurosurgery, Jinling Hospital, Nanjing, ChinaSchool of Medicine, Nanjing Medical University, Nanjing, ChinaBackgroundThe glioma-associated stromal cell (GASC) is a recently identified type of cell in the glioma microenvironment and may be a prognostic marker for glioma. However, the potential mechanisms of GASCs in the glioma microenvironment remain largely unknown. In this work, we aimed to explore the mechanisms of GASCs in gliomas, particularly in high-grade gliomas (HGG).MethodsWe used glioma datasets from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We utilized the Single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm to discriminate between patients with high or low GASC composition. The xCELL and CIBERSORT algorithms were used to analyze the composition of stromal cells and immune cells. Risk score and a nomogram model were constructed for prognostic prediction of glioma.ResultsWe observed for the first time that the levels of M2 macrophages and immune checkpoints (PD-1, PD-L1, PD-L2, TIM3, Galectin-9, CTLA-4, CD80, CD86, CD155, and CIITA) were significantly higher in the high GASC group and showed positive correlation with the GASC score in all glioma population and the HGG population. Copy number variations of DR3 and CIITA were higher in the high-GASC group. THY1, one of the GASC markers, exhibited lower methylation in the high GASC group. The constructed risk score was an independent predictor of glioma prognostics. Finally, a credible nomogram based on the risk score was established.ConclusionsGASCs stimulate glioma malignancy through the M2 macrophage, and are associated with the level of immune checkpoints in the glioma microenvironment. The methylation of THY1 could be used as prognostic indicator and treatment target for glioma. However, further studies are required to verify these findings.https://www.frontiersin.org/articles/10.3389/fonc.2021.672928/fullgliomaglioma-associated stromal cellimmune check pointsM2 macrophagestumor microenvironment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiangming Cai Feng Yuan Feng Yuan Junhao Zhu Jin Yang Chao Tang Zixiang Cong Zixiang Cong Chiyuan Ma Chiyuan Ma Chiyuan Ma Chiyuan Ma |
spellingShingle |
Xiangming Cai Feng Yuan Feng Yuan Junhao Zhu Jin Yang Chao Tang Zixiang Cong Zixiang Cong Chiyuan Ma Chiyuan Ma Chiyuan Ma Chiyuan Ma Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune Microenvironment Frontiers in Oncology glioma glioma-associated stromal cell immune check points M2 macrophages tumor microenvironment |
author_facet |
Xiangming Cai Feng Yuan Feng Yuan Junhao Zhu Jin Yang Chao Tang Zixiang Cong Zixiang Cong Chiyuan Ma Chiyuan Ma Chiyuan Ma Chiyuan Ma |
author_sort |
Xiangming Cai |
title |
Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune Microenvironment |
title_short |
Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune Microenvironment |
title_full |
Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune Microenvironment |
title_fullStr |
Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune Microenvironment |
title_full_unstemmed |
Glioma-Associated Stromal Cells Stimulate Glioma Malignancy by Regulating the Tumor Immune Microenvironment |
title_sort |
glioma-associated stromal cells stimulate glioma malignancy by regulating the tumor immune microenvironment |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-04-01 |
description |
BackgroundThe glioma-associated stromal cell (GASC) is a recently identified type of cell in the glioma microenvironment and may be a prognostic marker for glioma. However, the potential mechanisms of GASCs in the glioma microenvironment remain largely unknown. In this work, we aimed to explore the mechanisms of GASCs in gliomas, particularly in high-grade gliomas (HGG).MethodsWe used glioma datasets from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We utilized the Single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm to discriminate between patients with high or low GASC composition. The xCELL and CIBERSORT algorithms were used to analyze the composition of stromal cells and immune cells. Risk score and a nomogram model were constructed for prognostic prediction of glioma.ResultsWe observed for the first time that the levels of M2 macrophages and immune checkpoints (PD-1, PD-L1, PD-L2, TIM3, Galectin-9, CTLA-4, CD80, CD86, CD155, and CIITA) were significantly higher in the high GASC group and showed positive correlation with the GASC score in all glioma population and the HGG population. Copy number variations of DR3 and CIITA were higher in the high-GASC group. THY1, one of the GASC markers, exhibited lower methylation in the high GASC group. The constructed risk score was an independent predictor of glioma prognostics. Finally, a credible nomogram based on the risk score was established.ConclusionsGASCs stimulate glioma malignancy through the M2 macrophage, and are associated with the level of immune checkpoints in the glioma microenvironment. The methylation of THY1 could be used as prognostic indicator and treatment target for glioma. However, further studies are required to verify these findings. |
topic |
glioma glioma-associated stromal cell immune check points M2 macrophages tumor microenvironment |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.672928/full |
work_keys_str_mv |
AT xiangmingcai gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT fengyuan gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT fengyuan gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT junhaozhu gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT jinyang gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT chaotang gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT zixiangcong gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT zixiangcong gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT chiyuanma gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT chiyuanma gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT chiyuanma gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment AT chiyuanma gliomaassociatedstromalcellsstimulategliomamalignancybyregulatingthetumorimmunemicroenvironment |
_version_ |
1721501328755130368 |