Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development
BackgroundAlthough 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 tr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.738435/full |
| _version_ | 1819136266270146560 |
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| author | Shuai Ma Shuai Ma Yixu Ba Yixu Ba Hang Ji Hang Ji Fang Wang Jianyang Du Shaoshan Hu Shaoshan Hu |
| author_facet | Shuai Ma Shuai Ma Yixu Ba Yixu Ba Hang Ji Hang Ji Fang Wang Jianyang Du Shaoshan Hu Shaoshan Hu |
| author_sort | Shuai Ma |
| collection | DOAJ |
| description | BackgroundAlthough 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.MethodsGene 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.ResultsFour 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.ConclusionTP53, 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. |
| first_indexed | 2024-12-22T10:32:15Z |
| format | Article |
| id | doaj.art-37b862405663437e973593a8716d9694 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T10:32:15Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-37b862405663437e973593a8716d96942022-12-21T18:29:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.738435738435Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine DevelopmentShuai Ma0Shuai Ma1Yixu Ba2Yixu Ba3Hang Ji4Hang Ji5Fang Wang6Jianyang Du7Shaoshan Hu8Shaoshan Hu9Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaTranslational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Emergency Medicine Center, Zhejiang Provincial People's Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaBackgroundAlthough 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.MethodsGene 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.ResultsFour 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.ConclusionTP53, 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.738435/fullmRNA vaccineimmune subtypegliomaimmune landscapetumor antigens |
| spellingShingle | Shuai Ma Shuai Ma Yixu Ba Yixu Ba Hang Ji Hang Ji Fang Wang Jianyang Du Shaoshan Hu Shaoshan Hu Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development Frontiers in Immunology mRNA vaccine immune subtype glioma immune landscape tumor antigens |
| 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 | mRNA vaccine immune subtype glioma immune landscape tumor antigens |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.738435/full |
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