Identification of tumor antigens and immune subtypes in head and neck squamous cell carcinoma for mRNA vaccine development

The mRNA vaccines have been considered effective for combating cancer. However, the core components of the mRNA vaccines against head and neck squamous cell carcinoma (HNSCC) and the effects remain unclear. Our study aims to identify effective antigens in HNSCC to develop mRNA vaccines for corresponding potential patients. Here, we analyzed alternative splicing and mutation of genes in TCGA-HNSCC samples and identified seven potential tumor antigens, including SREBF1, LUC7L3, LAMA5, PCGF3, HNRNPH1, KLC4, and OFD1, which were associated with nonsense-mediated mRNA decay factor expression, overall survival prognosis and the infiltration of antigen-presenting cells. Furthermore, to select suitable patients for vaccination, immune subtypes related to HNSCC were identified by consensus clustering analysis, and visualization of the HNSCC immune landscape was performed by graph-learning-based dimensionality reduction. To address the heterogeneity of the population that is suitable for vaccination, plot cell trajectory and WGCNA were also utilized. HNSCC patients were classified into three prognostically relevant immune subtypes (Cluster 1, Cluster 2, and Cluster 3) possessing different molecular and cellular characteristics, immune modulators, and mutation statuses. Cluster 1 had an immune-activated phenotype and was associated with better survival, while Cluster 2 and Cluster 3 were immunologically cold and linked to increased tumor mutation burden. Therefore, HNSCC patients with immune subtypes Cluster 2 and Cluster 3 are potentially suitable for mRNA vaccination. Moreover, the prognostic module hub genes screened seven genes, including IGKC, IGHV3-15, IGLV1-40, IGLV1-51, IGLC3, IGLC2, and CD79A, which could be potential biomarkers to predict prognosis and identify suitable patients for mRNA vaccines. Our findings provide a theoretical basis for further research and the development of anti-HNSCC mRNA vaccines and the selection of suitable patients for vaccination.