Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival.
Genome Res
; 24(5): 743-50, 2014 May.
Article
em En
| MEDLINE
| ID: mdl-24782321
ABSTRACT
Somatic missense mutations can initiate tumorogenesis and, conversely, anti-tumor cytotoxic T cell (CTL) responses. Tumor genome analysis has revealed extreme heterogeneity among tumor missense mutation profiles, but their relevance to tumor immunology and patient outcomes has awaited comprehensive evaluation. Here, for 515 patients from six tumor sites, we used RNA-seq data from The Cancer Genome Atlas to identify mutations that are predicted to be immunogenic in that they yielded mutational epitopes presented by the MHC proteins encoded by each patient's autologous HLA-A alleles. Mutational epitopes were associated with increased patient survival. Moreover, the corresponding tumors had higher CTL content, inferred from CD8A gene expression, and elevated expression of the CTL exhaustion markers PDCD1 and CTLA4. Mutational epitopes were very scarce in tumors without evidence of CTL infiltration. These findings suggest that the abundance of predicted immunogenic mutations may be useful for identifying patients likely to benefit from checkpoint blockade and related immunotherapies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
/
Complexo Principal de Histocompatibilidade
/
Antígenos de Neoplasias
/
Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Genome Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2014
Tipo de documento:
Article