Tumor antigens and immunogenic cell death subtypes guided mRNA vaccine development for lower-grade gliomas

Abstract

Abstract Background: Accumulating evidence demonstrated the effectiveness of mRNA vaccine against many cancers, however, their development in LGGs is still urgently needed. In addition, increasing evidence demonstrated that Immunogenic cell death (ICD) was associated with antitumor immune response. Thus, the aim of our study was to identify potential LGG tumor antigens for mRNA vaccine development and select suitable patients for vaccination based on ICD subtypes. Methods: Gene expression matrix and matched clinical information of LGG were downloaded from the UCSC Xena website and CGGA databases. Differential expression analysis was conducted by GEPIA, and altered genomes were obtained from cBioPortal. TIMER was used for immune cell infiltration analysis, consensus clustering for typing ICD subtypes, and WGCNA for identifying hub modules and genes related to ICD subtypes. Eighty-two glioma tissue samples were collected and immunohistochemical staining was used to validate the correlation between tumor antigens and co-stimulatory factors. Results: We identified seven potential LGG tumor antigens significantly correlated with poor prognosis and strongly positively correlated with infiltration of antigen-presenting cells, including CREB3L2, DDR2, IRF2, NCSTN, RECQL, REST, and TGFBR1. Furthermore, we identified two ICD subtypes in LGGs with different clinical, cellular, and molecular characteristics. Icds1 is an immunological "hot" and immunosuppression phenotype with a worse prognosis, while Icds2 is an immunological cold phenotype with a better prognosis. Finally, WGCNA identified hub immune-related genes associated with ICD subtypes, which could be potential vaccination biomarkers. Conclusion: In summary, CREB3L2, DDR2, IRF2, NCSTN, RECQL, REST, and TGFBR1 are LGGs’ potential tumor antigens for mRNA vaccine development. The Icds2 subtype is suitable for vaccination.