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Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival
Improvement of risk stratification through prognostic biomarkers may enhance the personalization of cancer patient monitoring and treatment. We used Ancer, an immunoinformatic CD8, CD4, and regulatory T cell neoepitope screening system, to perform an advanced neoantigen analysis of genomic data deri...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113358/ https://www.ncbi.nlm.nih.gov/pubmed/33976291 http://dx.doi.org/10.1038/s41598-021-89016-7 |
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author | Richard, Guilhem De Groot, Anne S. Steinberg, Gary D. Garcia, Tzintzuni I. Kacew, Alec Ardito, Matthew Martin, William D. Berdugo, Gad Princiotta, Michael F. Balar, Arjun V. Sweis, Randy F. |
author_facet | Richard, Guilhem De Groot, Anne S. Steinberg, Gary D. Garcia, Tzintzuni I. Kacew, Alec Ardito, Matthew Martin, William D. Berdugo, Gad Princiotta, Michael F. Balar, Arjun V. Sweis, Randy F. |
author_sort | Richard, Guilhem |
collection | PubMed |
description | Improvement of risk stratification through prognostic biomarkers may enhance the personalization of cancer patient monitoring and treatment. We used Ancer, an immunoinformatic CD8, CD4, and regulatory T cell neoepitope screening system, to perform an advanced neoantigen analysis of genomic data derived from the urothelial cancer cohort of The Cancer Genome Atlas. Ancer demonstrated improved prognostic stratification and five-year survival prediction compared to standard analyses using tumor mutational burden or neoepitope identification using NetMHCpan and NetMHCIIpan. The superiority of Ancer, shown in both univariate and multivariate survival analyses, is attributed to the removal of neoepitopes that do not contribute to tumor immunogenicity based on their homology with self-epitopes. This analysis suggests that the presence of a higher number of unique, non-self CD8- and CD4-neoepitopes contributes to cancer survival, and that prospectively defining these neoepitopes using Ancer is a novel prognostic or predictive biomarker. |
format | Online Article Text |
id | pubmed-8113358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81133582021-05-12 Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival Richard, Guilhem De Groot, Anne S. Steinberg, Gary D. Garcia, Tzintzuni I. Kacew, Alec Ardito, Matthew Martin, William D. Berdugo, Gad Princiotta, Michael F. Balar, Arjun V. Sweis, Randy F. Sci Rep Article Improvement of risk stratification through prognostic biomarkers may enhance the personalization of cancer patient monitoring and treatment. We used Ancer, an immunoinformatic CD8, CD4, and regulatory T cell neoepitope screening system, to perform an advanced neoantigen analysis of genomic data derived from the urothelial cancer cohort of The Cancer Genome Atlas. Ancer demonstrated improved prognostic stratification and five-year survival prediction compared to standard analyses using tumor mutational burden or neoepitope identification using NetMHCpan and NetMHCIIpan. The superiority of Ancer, shown in both univariate and multivariate survival analyses, is attributed to the removal of neoepitopes that do not contribute to tumor immunogenicity based on their homology with self-epitopes. This analysis suggests that the presence of a higher number of unique, non-self CD8- and CD4-neoepitopes contributes to cancer survival, and that prospectively defining these neoepitopes using Ancer is a novel prognostic or predictive biomarker. Nature Publishing Group UK 2021-05-11 /pmc/articles/PMC8113358/ /pubmed/33976291 http://dx.doi.org/10.1038/s41598-021-89016-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Richard, Guilhem De Groot, Anne S. Steinberg, Gary D. Garcia, Tzintzuni I. Kacew, Alec Ardito, Matthew Martin, William D. Berdugo, Gad Princiotta, Michael F. Balar, Arjun V. Sweis, Randy F. Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival |
title | Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival |
title_full | Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival |
title_fullStr | Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival |
title_full_unstemmed | Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival |
title_short | Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival |
title_sort | multi-step screening of neoantigens’ hla- and tcr-interfaces improves prediction of survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113358/ https://www.ncbi.nlm.nih.gov/pubmed/33976291 http://dx.doi.org/10.1038/s41598-021-89016-7 |
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