Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development
Abstract Background As an important part of tumor immunotherapy for adjunct, therapeutic tumor vaccines have been effective against multiple solid cancers, while their efficacy against lower grade glioma (LGG) remains undefined. Immunophenotyping of tumors is an essential tool to evaluate the immune...
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doaj-068ddba0e97d45e99c6ed7ea88ac19452021-08-22T11:09:30ZengBMCJournal of Translational Medicine1479-58762021-08-0119111310.1186/s12967-021-03014-xIdentification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine developmentLiguo Ye0Long Wang1Ji’an Yang2Ping Hu3Chunyu Zhang4Shi’ao Tong5Zhennan Liu6Daofeng Tian7Department of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityAbstract Background As an important part of tumor immunotherapy for adjunct, therapeutic tumor vaccines have been effective against multiple solid cancers, while their efficacy against lower grade glioma (LGG) remains undefined. Immunophenotyping of tumors is an essential tool to evaluate the immune function of patients with immunodeficiency or autoimmunity. Therefore, this study aims to find the potential tumor antigen of LGG and identify the suitable population for cancer vaccination based on the immune landscape. Method The genomic and clinical data of 529 patients with LGG were obtained from TCGA, the mRNA_seq data of normal brain tissue were downloaded from GTEx. Differential expression gene and mutation analysis were performed to screen out potential antigens, K-M curves were carried out to investigate the correlation between the level of potential antigens and OS and DFS of patients. TIMER dataset was used to explore the correlation between genes and immune infiltrating cells. Immunophenotyping of 529 tumor samples was based on the single-sample gene sets enrichment analysis. Cibersort and Estimate algorithm were used to explore the tumor immune microenvironment characteristics in each immune subtype. Weighted gene co-expression network analysis (WGCNA) clustered immune-related genes and screened the hub genes, and pathway enrichment analyses were performed on the hub modules related to immune subtype in the WGCNA. Results Selecting for the mutated, up-regulated, prognosis- and immune-related genes, four potential tumor antigens were identified in LGG. They were also significantly positively associated with the antigen-presenting immune cells (APCs). Three robust immune subtypes, IS1, IS2 and IS3, represented immune status "desert", "immune inhibition", and "inflamed" respectively, which might serve as a predictive parameter. Subsequently, clinicopathological features, including the codeletion status of 1p19q, IDH mutation status, tumor mutation burden, tumor stemness, etc., were significantly different among subtypes. Conclusion FCGBP, FLNC, TLR7, and CSF2RA were potential antigens for developing cancer vaccination, and the patients in IS3 were considered the most suitable for vaccination in LGG.https://doi.org/10.1186/s12967-021-03014-xLower grade gliomaTumor antigensImmunotypingCancer vaccinationBioinformatics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Liguo Ye Long Wang Ji’an Yang Ping Hu Chunyu Zhang Shi’ao Tong Zhennan Liu Daofeng Tian |
spellingShingle |
Liguo Ye Long Wang Ji’an Yang Ping Hu Chunyu Zhang Shi’ao Tong Zhennan Liu Daofeng Tian Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development Journal of Translational Medicine Lower grade glioma Tumor antigens Immunotyping Cancer vaccination Bioinformatics |
author_facet |
Liguo Ye Long Wang Ji’an Yang Ping Hu Chunyu Zhang Shi’ao Tong Zhennan Liu Daofeng Tian |
author_sort |
Liguo Ye |
title |
Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development |
title_short |
Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development |
title_full |
Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development |
title_fullStr |
Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development |
title_full_unstemmed |
Identification of tumor antigens and immune subtypes in lower grade gliomas for mRNA vaccine development |
title_sort |
identification of tumor antigens and immune subtypes in lower grade gliomas for mrna vaccine development |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2021-08-01 |
description |
Abstract Background As an important part of tumor immunotherapy for adjunct, therapeutic tumor vaccines have been effective against multiple solid cancers, while their efficacy against lower grade glioma (LGG) remains undefined. Immunophenotyping of tumors is an essential tool to evaluate the immune function of patients with immunodeficiency or autoimmunity. Therefore, this study aims to find the potential tumor antigen of LGG and identify the suitable population for cancer vaccination based on the immune landscape. Method The genomic and clinical data of 529 patients with LGG were obtained from TCGA, the mRNA_seq data of normal brain tissue were downloaded from GTEx. Differential expression gene and mutation analysis were performed to screen out potential antigens, K-M curves were carried out to investigate the correlation between the level of potential antigens and OS and DFS of patients. TIMER dataset was used to explore the correlation between genes and immune infiltrating cells. Immunophenotyping of 529 tumor samples was based on the single-sample gene sets enrichment analysis. Cibersort and Estimate algorithm were used to explore the tumor immune microenvironment characteristics in each immune subtype. Weighted gene co-expression network analysis (WGCNA) clustered immune-related genes and screened the hub genes, and pathway enrichment analyses were performed on the hub modules related to immune subtype in the WGCNA. Results Selecting for the mutated, up-regulated, prognosis- and immune-related genes, four potential tumor antigens were identified in LGG. They were also significantly positively associated with the antigen-presenting immune cells (APCs). Three robust immune subtypes, IS1, IS2 and IS3, represented immune status "desert", "immune inhibition", and "inflamed" respectively, which might serve as a predictive parameter. Subsequently, clinicopathological features, including the codeletion status of 1p19q, IDH mutation status, tumor mutation burden, tumor stemness, etc., were significantly different among subtypes. Conclusion FCGBP, FLNC, TLR7, and CSF2RA were potential antigens for developing cancer vaccination, and the patients in IS3 were considered the most suitable for vaccination in LGG. |
topic |
Lower grade glioma Tumor antigens Immunotyping Cancer vaccination Bioinformatics |
url |
https://doi.org/10.1186/s12967-021-03014-x |
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