In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma
BackgroundMutations commonly occur in cancer cells, arising neoantigen as potential targets for personalized immunotherapy of lung adenocarcinoma (LUAD). However, the substantial heterogeneity observed among individuals and distinct foci within the same patient presents significant challenges in for...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456209/full |
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| author | Xin Wang Lang Jiang Juan Zhao Mi Wu Jin Xiong Xiongwen Wu Xiufang Weng |
| author_facet | Xin Wang Lang Jiang Juan Zhao Mi Wu Jin Xiong Xiongwen Wu Xiufang Weng |
| author_sort | Xin Wang |
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| description | BackgroundMutations commonly occur in cancer cells, arising neoantigen as potential targets for personalized immunotherapy of lung adenocarcinoma (LUAD). However, the substantial heterogeneity observed among individuals and distinct foci within the same patient presents significant challenges in formulating immunotherapy strategies. The aim of the work is to characterize the mutation pattern and identify neopeptides across different patients and diverse foci within the same patients with LUAD.MethodsSeven lung adenocarcinoma samples and matched tissues/blood are collected from 4 patients with LUAD for whole exome sequencing, mutation signature analysis, HLA binding prediction and neoantigen screening. Dimeric HLA-A2 molecules were prepared by Bac-to-Bac baculovirus expression system to establish a T cell stimulation system based on HLA-A2-coated artificial antigen-presenting cells for the validation of immunogenic neopeptides.ResultsSimilar mutation pattern with predominant missense mutation and high tumor mutation burden was observed across individuals with lung adenocarcinomas and between non-invasive and invasive foci. We screened and identified 3 consistent mutated genes among 100 top genes with highest mutation scores contributed across 4 patients, and 3 mutated peptides among 30 with highest HLA-A2 binding affinity distributed in at least 2 out of 4 foci in the same patient. Notably, LUAD-7-MT peptide encoded by NANOGNB demonstrated higher immunogenicity in promoting CD8+ T cells proliferation and IFN-γ secretion than the corresponding wildtype peptide.ConclusionsThis study provides an in-depth analysis of mutation characteristics of LUAD and establishes a neoantigen screening and validation system for identifying immunogenicity neopeptide across individual patients and diverse foci in the same patient with multifocal LUAD. |
| format | Article |
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| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-b668bdda63f74cbeaff29830842dff3d2025-08-20T02:22:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14562091456209In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinomaXin Wang0Lang Jiang1Juan Zhao2Mi Wu3Jin Xiong4Xiongwen Wu5Xiufang Weng6Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackgroundMutations commonly occur in cancer cells, arising neoantigen as potential targets for personalized immunotherapy of lung adenocarcinoma (LUAD). However, the substantial heterogeneity observed among individuals and distinct foci within the same patient presents significant challenges in formulating immunotherapy strategies. The aim of the work is to characterize the mutation pattern and identify neopeptides across different patients and diverse foci within the same patients with LUAD.MethodsSeven lung adenocarcinoma samples and matched tissues/blood are collected from 4 patients with LUAD for whole exome sequencing, mutation signature analysis, HLA binding prediction and neoantigen screening. Dimeric HLA-A2 molecules were prepared by Bac-to-Bac baculovirus expression system to establish a T cell stimulation system based on HLA-A2-coated artificial antigen-presenting cells for the validation of immunogenic neopeptides.ResultsSimilar mutation pattern with predominant missense mutation and high tumor mutation burden was observed across individuals with lung adenocarcinomas and between non-invasive and invasive foci. We screened and identified 3 consistent mutated genes among 100 top genes with highest mutation scores contributed across 4 patients, and 3 mutated peptides among 30 with highest HLA-A2 binding affinity distributed in at least 2 out of 4 foci in the same patient. Notably, LUAD-7-MT peptide encoded by NANOGNB demonstrated higher immunogenicity in promoting CD8+ T cells proliferation and IFN-γ secretion than the corresponding wildtype peptide.ConclusionsThis study provides an in-depth analysis of mutation characteristics of LUAD and establishes a neoantigen screening and validation system for identifying immunogenicity neopeptide across individual patients and diverse foci in the same patient with multifocal LUAD.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456209/fullneopeptide screeningmultifocal lung adenocarcinomaNANOGNBimmunogenicity neopeptideartificial antigen-presenting cells |
| spellingShingle | Xin Wang Lang Jiang Juan Zhao Mi Wu Jin Xiong Xiongwen Wu Xiufang Weng In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma Frontiers in Immunology neopeptide screening multifocal lung adenocarcinoma NANOGNB immunogenicity neopeptide artificial antigen-presenting cells |
| title | In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma |
| title_full | In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma |
| title_fullStr | In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma |
| title_full_unstemmed | In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma |
| title_short | In silico neoantigen screening and HLA multimer-based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma |
| title_sort | in silico neoantigen screening and hla multimer based validation identify immunogenic neopeptide in multifocal lung adenocarcinoma |
| topic | neopeptide screening multifocal lung adenocarcinoma NANOGNB immunogenicity neopeptide artificial antigen-presenting cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456209/full |
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