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Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development
BACKGROUND: Although mRNA vaccines have been efficient for combating a variety of tumors, their effectiveness against glioma remains unclear. There is growing evidence that immunophenotyping can reflect the comprehensive immune status and microenvironment of the tumor, which correlates closely with...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484904/ https://www.ncbi.nlm.nih.gov/pubmed/34603319 http://dx.doi.org/10.3389/fimmu.2021.738435 |
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author | Ma, Shuai Ba, Yixu Ji, Hang Wang, Fang Du, Jianyang Hu, Shaoshan |
author_facet | Ma, Shuai Ba, Yixu Ji, Hang Wang, Fang Du, Jianyang Hu, Shaoshan |
author_sort | Ma, Shuai |
collection | PubMed |
description | BACKGROUND: Although mRNA vaccines have been efficient for combating a variety of tumors, their effectiveness against glioma remains unclear. There is growing evidence that immunophenotyping can reflect the comprehensive immune status and microenvironment of the tumor, which correlates closely with treatment response and vaccination potency. The purpose of this research was to screen for effective antigens in glioma that could be used for developing mRNA vaccines and to further differentiate the immune subtypes of glioma to create an selection criteria for suitable patients for vaccination. METHODS: Gene expression profiles and clinical data of 698 glioma samples were extracted from The Cancer Genome Atlas, and RNA_seq data of 1018 glioma samples was gathered from Chinese Glioma Genome Atlas. Gene Expression Profiling Interactive Analysis was used to determine differential expression genes and prognostic markers, cBioPortal software was used to verify gene alterations, and Tumor Immune Estimation Resource was used to investigate the relationships among genes and immune infiltrating cells. Consistency clustering was applied for consistent matrix construction and data aggregation, Gene oncology enrichment was performed for functional annotation, and a graph learning-based dimensionality reduction method was applied to describe the subtypes of immunity. RESULTS: Four overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in glioma, including TP53, IDH1, C3, and TCF12. Besides, four immune subtypes of glioma (IS1-IS4) and 10 immune gene modules were identified consistently in the TCGA data. The immune subtypes had diverse molecular, cellular, and clinical features. IS1 and IS4 displayed an immune-activating phenotype and were associated with worse survival than the other two subtypes, while IS2 and IS3 had lower levels of tumor immune infiltration. Immunogenic cell death regulators and immune checkpoints were also diversely expressed in the four immune subtypes. CONCLUSION: TP53, IDH1, C3, and TCF12 are effective antigens for the development of anti-glioma mRNA vaccines. We found four stable and repeatable immune subtypes of human glioma, the classification of the immune subtypes of glioma may play a crucial role in the predicting mRNA vaccine outcome. |
format | Online Article Text |
id | pubmed-8484904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84849042021-10-02 Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development Ma, Shuai Ba, Yixu Ji, Hang Wang, Fang Du, Jianyang Hu, Shaoshan Front Immunol Immunology BACKGROUND: Although mRNA vaccines have been efficient for combating a variety of tumors, their effectiveness against glioma remains unclear. There is growing evidence that immunophenotyping can reflect the comprehensive immune status and microenvironment of the tumor, which correlates closely with treatment response and vaccination potency. The purpose of this research was to screen for effective antigens in glioma that could be used for developing mRNA vaccines and to further differentiate the immune subtypes of glioma to create an selection criteria for suitable patients for vaccination. METHODS: Gene expression profiles and clinical data of 698 glioma samples were extracted from The Cancer Genome Atlas, and RNA_seq data of 1018 glioma samples was gathered from Chinese Glioma Genome Atlas. Gene Expression Profiling Interactive Analysis was used to determine differential expression genes and prognostic markers, cBioPortal software was used to verify gene alterations, and Tumor Immune Estimation Resource was used to investigate the relationships among genes and immune infiltrating cells. Consistency clustering was applied for consistent matrix construction and data aggregation, Gene oncology enrichment was performed for functional annotation, and a graph learning-based dimensionality reduction method was applied to describe the subtypes of immunity. RESULTS: Four overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in glioma, including TP53, IDH1, C3, and TCF12. Besides, four immune subtypes of glioma (IS1-IS4) and 10 immune gene modules were identified consistently in the TCGA data. The immune subtypes had diverse molecular, cellular, and clinical features. IS1 and IS4 displayed an immune-activating phenotype and were associated with worse survival than the other two subtypes, while IS2 and IS3 had lower levels of tumor immune infiltration. Immunogenic cell death regulators and immune checkpoints were also diversely expressed in the four immune subtypes. CONCLUSION: TP53, IDH1, C3, and TCF12 are effective antigens for the development of anti-glioma mRNA vaccines. We found four stable and repeatable immune subtypes of human glioma, the classification of the immune subtypes of glioma may play a crucial role in the predicting mRNA vaccine outcome. Frontiers Media S.A. 2021-09-17 /pmc/articles/PMC8484904/ /pubmed/34603319 http://dx.doi.org/10.3389/fimmu.2021.738435 Text en Copyright © 2021 Ma, Ba, Ji, Wang, Du and Hu 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 Ma, Shuai Ba, Yixu Ji, Hang Wang, Fang Du, Jianyang Hu, Shaoshan Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development |
title | Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development |
title_full | Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development |
title_fullStr | Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development |
title_full_unstemmed | Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development |
title_short | Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development |
title_sort | recognition of tumor-associated antigens and immune subtypes in glioma for mrna vaccine development |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484904/ https://www.ncbi.nlm.nih.gov/pubmed/34603319 http://dx.doi.org/10.3389/fimmu.2021.738435 |
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