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

SCANDINAVIAN JOURNAL OF IMMUNOLOGY(2023)

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摘要
Therapeutic application of vaccines to endometrial carcinoma (EC) remains uncertain. In this study, we aimed to identify potential tumour antigens for use in the development of an anti-tumour mRNA vaccine and clarify immune subtypes and their characteristics for immunotherapeutic application in heterogeneous EC by integrating multi-omics data. Importantly, four potential tumour 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 harboured 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 tumours. 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 tumour antigens can be used for developing antitumour mRNA vaccines, and tumours with C2 immunophenotypic characteristics demonstrated sensitivity and susceptibility to immunotherapy in EC.
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关键词
endometrial carcinoma,immune subtypes,tumour antigens
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