دورية أكاديمية
An Analysis of Natural T Cell Responses to Predicted Tumor Neoepitopes.
| العنوان: | An Analysis of Natural T Cell Responses to Predicted Tumor Neoepitopes. |
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| المؤلفون: | Bjerregaard AM; Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark., Nielsen M; Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark.; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina., Jurtz V; Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark., Barra CM; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina., Hadrup SR; Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Kongens Lyngby, Denmark., Szallasi Z; Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark.; Computational Health Informatics Program (CHIP), Boston Children's Hospital, Harvard Medical School, Boston, MA, United States., Eklund AC; Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark. |
| المصدر: | Frontiers in immunology [Front Immunol] 2017 Nov 15; Vol. 8, pp. 1566. Date of Electronic Publication: 2017 Nov 15 (Print Publication: 2017). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Print ISSN: 1664-3224 (Print) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مستخلص: | Personalization of cancer immunotherapies such as therapeutic vaccines and adoptive T-cell therapy may benefit from efficient identification and targeting of patient-specific neoepitopes. However, current neoepitope prediction methods based on sequencing and predictions of epitope processing and presentation result in a low rate of validation, suggesting that the determinants of peptide immunogenicity are not well understood. We gathered published data on human neopeptides originating from single amino acid substitutions for which T cell reactivity had been experimentally tested, including both immunogenic and non-immunogenic neopeptides. Out of 1,948 neopeptide-HLA (human leukocyte antigen) combinations from 13 publications, 53 were reported to elicit a T cell response. From these data, we found an enrichment for responses among peptides of length 9. Even though the peptides had been pre-selected based on presumed likelihood of being immunogenic, we found using NetMHCpan-4.0 that immunogenic neopeptides were predicted to bind significantly more strongly to HLA compared to non-immunogenic peptides. Investigation of the HLA binding strength of the immunogenic peptides revealed that the vast majority (96%) shared very strong predicted binding to HLA and that the binding strength was comparable to that observed for pathogen-derived epitopes. Finally, we found that neopeptide dissimilarity to self is a predictor of immunogenicity in situations where neo- and normal peptides share comparable predicted binding strength. In conclusion, these results suggest new strategies for prioritization of mutated peptides, but new data will be needed to confirm their value. |
| التعليقات: | Erratum in: Front Immunol. 2018 May 14;9:1007. (PMID: 29795801) |
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| فهرسة مساهمة: | Keywords: MHC binding; immunogenicity; mutations; neoantigens; neoepitopes; prediction |
| تواريخ الأحداث: | Date Created: 20171201 Latest Revision: 20210103 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC5694748 |
| DOI: | 10.3389/fimmu.2017.01566 |
| PMID: | 29187854 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2017.01566 |