Artículo
Unraveling tumor specific neoantigen immunogenicity prediction: a comprehensive analysis
Nibeyro, Guadalupe
; Baronetto, Verónica Mabel
; Folco, Juan I.; Pastore, Pablo Germán
; Girotti, Maria Romina
; Prato, Laura; Morón, Gabriel; Lujan, Hugo Daniel
; Fernandez, Elmer Andres
Fecha de publicación:
07/2023
Editorial:
Frontiers Media
Revista:
Frontiers in Immunology
ISSN:
1664-3224
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Introduction: Identification of tumor specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based anti-tumoral vaccines and/or adoptive T-cell immunotherapies; thus, accurate in-silico classification/prioritization proves critical for cost-effective clinical applications. Several methods were proposed as TSNs immunogenicity predictors; however, comprehensive performance comparison is still lacking due to the absence of well documented and adequate TSN databases. Methods: Here, by developing a new curated database having 199 TSNs with experimentally-validated MHC-I presentation and positive/negative immune response (ITSNdb), sixteen metrics were evaluated as immunogenicity predictors. In addition, by using a dataset emulating patient derived TSNs and immunotherapy cohorts containing predicted TSNs for tumor neoantigen burden (TNB) with outcome association, the metrics were evaluated as TSNs prioritizers and as immunotherapy response biomarkers. Results: Our results show high performance variability among methods, highlighting the need for substantial improvement. Deep learning predictors were top ranked on ITSNdb but show discrepancy on validation databases. In overall, current predicted TNB did not outperform existing biomarkers. Conclusion: Recommendations for their clinical application and the ITSNdb are presented to promote development and comparison of computational TSNs immunogenicity predictors.
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Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos(CIDIE)
Articulos de CENTRO DE INV. Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Articulos de CENTRO DE INV. Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Citación
Nibeyro, Guadalupe; Baronetto, Verónica Mabel; Folco, Juan I.; Pastore, Pablo Germán; Girotti, Maria Romina; et al.; Unraveling tumor specific neoantigen immunogenicity prediction: a comprehensive analysis; Frontiers Media; Frontiers in Immunology; 14; 7-2023; 1-11
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