Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival

Abstract 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...

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Autores principales:	Guilhem Richard, Anne S. De Groot, Gary D. Steinberg, Tzintzuni I. Garcia, Alec Kacew, Matthew Ardito, William D. Martin, Gad Berdugo, Michael F. Princiotta, Arjun V. Balar, Randy F. Sweis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d371f9d2ea90470a84bf2e9f0ded5167
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spelling	oai:doaj.org-article:d371f9d2ea90470a84bf2e9f0ded51672021-12-02T14:35:40ZMulti-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival10.1038/s41598-021-89016-72045-2322https://doaj.org/article/d371f9d2ea90470a84bf2e9f0ded51672021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89016-7https://doaj.org/toc/2045-2322Abstract 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.Guilhem RichardAnne S. De GrootGary D. SteinbergTzintzuni I. GarciaAlec KacewMatthew ArditoWilliam D. MartinGad BerdugoMichael F. PrinciottaArjun V. BalarRandy F. SweisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guilhem Richard Anne S. De Groot Gary D. Steinberg Tzintzuni I. Garcia Alec Kacew Matthew Ardito William D. Martin Gad Berdugo Michael F. Princiotta Arjun V. Balar Randy F. Sweis Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival
description	Abstract 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	article
author	Guilhem Richard Anne S. De Groot Gary D. Steinberg Tzintzuni I. Garcia Alec Kacew Matthew Ardito William D. Martin Gad Berdugo Michael F. Princiotta Arjun V. Balar Randy F. Sweis
author_facet	Guilhem Richard Anne S. De Groot Gary D. Steinberg Tzintzuni I. Garcia Alec Kacew Matthew Ardito William D. Martin Gad Berdugo Michael F. Princiotta Arjun V. Balar Randy F. Sweis
author_sort	Guilhem Richard
title	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_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_sort	multi-step screening of neoantigens’ hla- and tcr-interfaces improves prediction of survival
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d371f9d2ea90470a84bf2e9f0ded5167
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Multi-step screening of neoantigens’ HLA- and TCR-interfaces improves prediction of survival

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