Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development

Abstract

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.

Identification of Implications of Angiogenesis and m6A Modification on Immunosuppression and Therapeutic Sensitivity in Low-Grade Glioma by Network Computational Analysis of Subtypes and Signatures

“…Recently, multiple pharmacological studies have shown that compounds acting on multiple genes or molecular pathways need to be designed ( 48 – 51 ). In this study, we observed similar mechanisms among different compounds, which indicated that selective therapy could target the MAGs-related phenotype of LGG.…”

Multiomics Data Analysis and Identification of Immune-Related Prognostic Signatures With Potential Implications in Prognosis and Immune Checkpoint Blockade Therapy of Glioblastoma

“…For the above outcomes, we concluded that patients in both groups were associated with corresponding immune infiltration status. Related literature implies that immune infiltration status may also be associated with mutation ( 5 , 26 , 27 ). To investigate whether immune infiltration status was associated with mutation rates, we performed mutation rate analysis for both groups.…”

“…In recent years, different approaches for GBM have been investigated, among which immunotherapy is one of the most attractive approaches and is currently undergoing active research. Patients treated with immune checkpoint blockade therapy (ICB) have shown a longer survival than those receiving conventional therapy ( 4 , 5 ). But, the treatments are effective in only a minority of patients, most patients have a limited or no response to treatment, especially during GBM progression.…”

RNA modification in mRNA cancer vaccines

“…There are many studies on glioma immunotherapy through analyzing the relevant data. Four tumor antigens ( TCF12 , TP53 , C3 , and IDH1 ) were found to be associated with poor prognosis and infiltration of antigen-presenting cells [ 106 ], while those ( ANXA5 , FKBP10 , MSN , and PYGL ) with good prognosis [ 107 ]. For glioblastoma (GBM), the most common and aggressive malignant brain tumor in adults, Rose et al identified 11 specific potential targets for immunotherapy strategies by comparing surfaceomes between GBM cells and astrocytes [ 108 ].…”