دورية أكاديمية
Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma
| العنوان: | Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma |
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| المؤلفون: | Markus W. Löffler, Christopher Mohr, Leon Bichmann, Lena Katharina Freudenmann, Mathias Walzer, Christopher M. Schroeder, Nico Trautwein, Franz J. Hilke, Raphael S. Zinser, Lena Mühlenbruch, Daniel J. Kowalewski, Heiko Schuster, Marc Sturm, Jakob Matthes, Olaf Riess, Stefan Czemmel, Sven Nahnsen, Ingmar Königsrainer, Karolin Thiel, Silvio Nadalin, Stefan Beckert, Hans Bösmüller, Falko Fend, Ana Velic, Boris Maček, Sebastian P. Haen, Luigi Buonaguro, Oliver Kohlbacher, Stefan Stevanović, Alfred Königsrainer, HEPAVAC Consortium, Hans-Georg Rammensee |
| المصدر: | Genome Medicine, Vol 11, Iss 1, Pp 1-16 (2019) |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Medicine LCC:Genetics |
| مصطلحات موضوعية: | Hepatocellular carcinoma, HLA, HLA ligandomics, Immunoinformatics, Immunotherapy, Liver cancer, Medicine, Genetics, QH426-470 |
| الوصف: | Abstract Background Although mutated HLA ligands are considered ideal cancer-specific immunotherapy targets, evidence for their presentation is lacking in hepatocellular carcinomas (HCCs). Employing a unique multi-omics approach comprising a neoepitope identification pipeline, we assessed exome-derived mutations naturally presented as HLA class I ligands in HCCs. Methods In-depth multi-omics analyses included whole exome and transcriptome sequencing to define individual patient-specific search spaces of neoepitope candidates. Evidence for the natural presentation of mutated HLA ligands was investigated through an in silico pipeline integrating proteome and HLA ligandome profiling data. Results The approach was successfully validated in a state-of-the-art dataset from malignant melanoma, and despite multi-omics evidence for somatic mutations, mutated naturally presented HLA ligands remained elusive in HCCs. An analysis of extensive cancer datasets confirmed fundamental differences of tumor mutational burden in HCC and malignant melanoma, challenging the notion that exome-derived mutations contribute relevantly to the expectable neoepitope pool in malignancies with only few mutations. Conclusions This study suggests that exome-derived mutated HLA ligands appear to be rarely presented in HCCs, inter alia resulting from a low mutational burden as compared to other malignancies such as malignant melanoma. Our results therefore demand widening the target scope for personalized immunotherapy beyond this limited range of mutated neoepitopes, particularly for malignancies with similar or lower mutational burden. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1756-994X |
| Relation: | http://link.springer.com/article/10.1186/s13073-019-0636-8; https://doaj.org/toc/1756-994X |
| DOI: | 10.1186/s13073-019-0636-8 |
| URL الوصول: | https://doaj.org/article/09823055f7a9475c93077f42081ab4b7 |
| رقم الأكسشن: | edsdoj.09823055f7a9475c93077f42081ab4b7 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1756994X |
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| DOI: | 10.1186/s13073-019-0636-8 |