Identification of tumor antigens and immune subtypes in the development of an anti-cancer vaccine for endometrial carcinoma.

Therapeutic application of vaccines to endometrial carcinoma (EC) remains uncertain. In this study, we aimed to identify potential tumor antigens for use in the development of an anti-tumor mRNA vaccine and clarify immune subtypes and their characteristics for immunotherapeutic application in heterogeneous EC by integrating multi-omics data. Importantly, four potential tumor antigen candidates-PGR, RBPJ, PARVG, and MSX1-were identified and significantly correlated with better overall survival, disease-free survival, and distinct antigen-presenting cell infiltration in EC. In addition, two different immune subtypes by consensus clustering analysis of the immune-related genes were identified. Patients with C2 immunophenotypes exhibited superior survival outcomes and "hot" immunoreactivity and harbored higher microsatellite instability scores and tumoral mutation burden but lower copy-number variation burden. Furthermore, the distinct expression of immunogenic cell death modulators and differential microenvironmental characteristics of immune-cell infiltration were also revealed between C1 and C2 immune-subtype tumors. Enrichment analysis of the co-expression of immune-related genes showed enrichment in immune response, immune cell-mediated immunity, and antigen processing pathways. These results indicated that these identified tumor antigens can be used for developing antitumor mRNA vaccines, and tumors with C2 immunophenotypic characteristics demonstrated sensitivity and susceptibility to immunotherapy in EC.