Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival
Open Access
- 29 April 2014
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 24 (5), 743-750
- https://doi.org/10.1101/gr.165985.113
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.Keywords
This publication has 67 references indexed in Scilit:
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- Comprehensive genomic characterization of squamous cell lung cancersNature, 2012
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- Prognostic significance of tumor-infiltrating T cells in ovarian cancer: A meta-analysisGynecologic Oncology, 2012
- The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysisBritish Journal of Cancer, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Prediction of epitopes using neural network based methodsJournal of Immunological Methods, 2010
- Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiationNature Biotechnology, 2010
- NetMHCpan, a method for MHC class I binding prediction beyond humansImmunogenetics, 2008
- Comprehensive genomic characterization defines human glioblastoma genes and core pathwaysNature, 2008