Cargando…
A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources
SIMPLE SUMMARY: Tumor-specific antigens are ideal targets for cancer immunotherapy. Mass spectrometry, which is the main method that directly identifies neo-epitopes presented on tumor cells, focuses mainly on peptides derived from annotated protein-coding exomes. However, non-canonical peptides ari...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220843/ https://www.ncbi.nlm.nih.gov/pubmed/35740681 http://dx.doi.org/10.3390/cancers14123016 |
_version_ | 1784732472679858176 |
---|---|
author | Xiang, Haitao Zhang, Le Bu, Fanyu Guan, Xiangyu Chen, Lei Zhang, Haibo Zhao, Yuntong Chen, Huanyi Zhang, Weicong Li, Yijian Lee, Leo Jingyu Mei, Zhanlong Rao, Yuan Gu, Ying Hou, Yong Mu, Feng Dong, Xuan |
author_facet | Xiang, Haitao Zhang, Le Bu, Fanyu Guan, Xiangyu Chen, Lei Zhang, Haibo Zhao, Yuntong Chen, Huanyi Zhang, Weicong Li, Yijian Lee, Leo Jingyu Mei, Zhanlong Rao, Yuan Gu, Ying Hou, Yong Mu, Feng Dong, Xuan |
author_sort | Xiang, Haitao |
collection | PubMed |
description | SIMPLE SUMMARY: Tumor-specific antigens are ideal targets for cancer immunotherapy. Mass spectrometry, which is the main method that directly identifies neo-epitopes presented on tumor cells, focuses mainly on peptides derived from annotated protein-coding exomes. However, non-canonical peptides arising from alterations at genomic, transcriptional, and posttranslational levels have been identified in several pioneering studies, making it necessary to develop an integrated proteogenomic approach that can comprehensively identify neoantigens derived from all genomic regions. Our novel strategy combining database searches with a de novo peptide sequencing method accurately identified multiple types of non-canonical peptides in the colorectal cancer cell line, HCT116. This practical proteogenomic strategy can be applied to neoantigen discovery in clinical tumor samples, improving cancer immunotherapy. ABSTRACT: Tumor-specific antigens can activate T cell-based antitumor immune responses and are ideal targets for cancer immunotherapy. However, their identification is still challenging. Although mass spectrometry can directly identify human leukocyte antigen (HLA) binding peptides in tumor cells, it focuses on tumor-specific antigens derived from annotated protein-coding regions constituting only 1.5% of the genome. We developed a novel proteogenomic integration strategy to expand the breadth of tumor-specific epitopes derived from all genomic regions. Using the colorectal cancer cell line HCT116 as a model, we accurately identified 10,737 HLA-presented peptides, 1293 of which were non-canonical peptides that traditional database searches could not identify. Moreover, we found eight tumor neo-epitopes derived from somatic mutations, four of which were not previously reported. Our findings suggest that this new proteogenomic approach holds great promise for increasing the number of tumor-specific antigen candidates, potentially enlarging the tumor target pool and improving cancer immunotherapy. |
format | Online Article Text |
id | pubmed-9220843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92208432022-06-24 A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources Xiang, Haitao Zhang, Le Bu, Fanyu Guan, Xiangyu Chen, Lei Zhang, Haibo Zhao, Yuntong Chen, Huanyi Zhang, Weicong Li, Yijian Lee, Leo Jingyu Mei, Zhanlong Rao, Yuan Gu, Ying Hou, Yong Mu, Feng Dong, Xuan Cancers (Basel) Article SIMPLE SUMMARY: Tumor-specific antigens are ideal targets for cancer immunotherapy. Mass spectrometry, which is the main method that directly identifies neo-epitopes presented on tumor cells, focuses mainly on peptides derived from annotated protein-coding exomes. However, non-canonical peptides arising from alterations at genomic, transcriptional, and posttranslational levels have been identified in several pioneering studies, making it necessary to develop an integrated proteogenomic approach that can comprehensively identify neoantigens derived from all genomic regions. Our novel strategy combining database searches with a de novo peptide sequencing method accurately identified multiple types of non-canonical peptides in the colorectal cancer cell line, HCT116. This practical proteogenomic strategy can be applied to neoantigen discovery in clinical tumor samples, improving cancer immunotherapy. ABSTRACT: Tumor-specific antigens can activate T cell-based antitumor immune responses and are ideal targets for cancer immunotherapy. However, their identification is still challenging. Although mass spectrometry can directly identify human leukocyte antigen (HLA) binding peptides in tumor cells, it focuses on tumor-specific antigens derived from annotated protein-coding regions constituting only 1.5% of the genome. We developed a novel proteogenomic integration strategy to expand the breadth of tumor-specific epitopes derived from all genomic regions. Using the colorectal cancer cell line HCT116 as a model, we accurately identified 10,737 HLA-presented peptides, 1293 of which were non-canonical peptides that traditional database searches could not identify. Moreover, we found eight tumor neo-epitopes derived from somatic mutations, four of which were not previously reported. Our findings suggest that this new proteogenomic approach holds great promise for increasing the number of tumor-specific antigen candidates, potentially enlarging the tumor target pool and improving cancer immunotherapy. MDPI 2022-06-19 /pmc/articles/PMC9220843/ /pubmed/35740681 http://dx.doi.org/10.3390/cancers14123016 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Xiang, Haitao Zhang, Le Bu, Fanyu Guan, Xiangyu Chen, Lei Zhang, Haibo Zhao, Yuntong Chen, Huanyi Zhang, Weicong Li, Yijian Lee, Leo Jingyu Mei, Zhanlong Rao, Yuan Gu, Ying Hou, Yong Mu, Feng Dong, Xuan A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources |
title | A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources |
title_full | A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources |
title_fullStr | A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources |
title_full_unstemmed | A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources |
title_short | A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources |
title_sort | novel proteogenomic integration strategy expands the breadth of neo-epitope sources |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220843/ https://www.ncbi.nlm.nih.gov/pubmed/35740681 http://dx.doi.org/10.3390/cancers14123016 |
work_keys_str_mv | AT xianghaitao anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhangle anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT bufanyu anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT guanxiangyu anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT chenlei anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhanghaibo anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhaoyuntong anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT chenhuanyi anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhangweicong anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT liyijian anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT leeleojingyu anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT meizhanlong anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT raoyuan anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT guying anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT houyong anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT mufeng anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT dongxuan anovelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT xianghaitao novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhangle novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT bufanyu novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT guanxiangyu novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT chenlei novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhanghaibo novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhaoyuntong novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT chenhuanyi novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT zhangweicong novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT liyijian novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT leeleojingyu novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT meizhanlong novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT raoyuan novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT guying novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT houyong novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT mufeng novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources AT dongxuan novelproteogenomicintegrationstrategyexpandsthebreadthofneoepitopesources |