Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to pri...

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Autores principales:	Wentao Fang, Chia-Hsin Wu, Qiang-Ling Sun, Zhi-Tao Gu, Lei Zhu, Teng Mao, Xue-Fei Zhang, Ning Xu, Tzu-Pin Lu, Mong-Hsun Tsai, Li-Han Chen, Liang-Chuan Lai, Eric Y. Chuang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	thymic carcinoma (TC) whole-exome sequencing (WES) RNA sequencing (RNAseq) immunotherapy neoantigen immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/22f1c15fdbbf44fdba19a94394394d98
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spelling	oai:doaj.org-article:22f1c15fdbbf44fdba19a94394394d982021-11-16T07:31:57ZNovel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas1664-322410.3389/fimmu.2021.748820https://doaj.org/article/22f1c15fdbbf44fdba19a94394394d982021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.748820/fullhttps://doaj.org/toc/1664-3224Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.Wentao FangChia-Hsin WuQiang-Ling SunQiang-Ling SunZhi-Tao GuLei ZhuTeng MaoXue-Fei ZhangNing XuTzu-Pin LuTzu-Pin LuMong-Hsun TsaiMong-Hsun TsaiLi-Han ChenLiang-Chuan LaiLiang-Chuan LaiEric Y. ChuangEric Y. ChuangEric Y. ChuangEric Y. ChuangFrontiers Media S.A.articlethymic carcinoma (TC)whole-exome sequencing (WES)RNA sequencing (RNAseq)immunotherapyneoantigenimmune checkpoint inhibitor (ICI)Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	thymic carcinoma (TC) whole-exome sequencing (WES) RNA sequencing (RNAseq) immunotherapy neoantigen immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy RC581-607
spellingShingle	thymic carcinoma (TC) whole-exome sequencing (WES) RNA sequencing (RNAseq) immunotherapy neoantigen immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy RC581-607 Wentao Fang Chia-Hsin Wu Qiang-Ling Sun Qiang-Ling Sun Zhi-Tao Gu Lei Zhu Teng Mao Xue-Fei Zhang Ning Xu Tzu-Pin Lu Tzu-Pin Lu Mong-Hsun Tsai Mong-Hsun Tsai Li-Han Chen Liang-Chuan Lai Liang-Chuan Lai Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas
description	Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.
format	article
author	Wentao Fang Chia-Hsin Wu Qiang-Ling Sun Qiang-Ling Sun Zhi-Tao Gu Lei Zhu Teng Mao Xue-Fei Zhang Ning Xu Tzu-Pin Lu Tzu-Pin Lu Mong-Hsun Tsai Mong-Hsun Tsai Li-Han Chen Liang-Chuan Lai Liang-Chuan Lai Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang
author_facet	Wentao Fang Chia-Hsin Wu Qiang-Ling Sun Qiang-Ling Sun Zhi-Tao Gu Lei Zhu Teng Mao Xue-Fei Zhang Ning Xu Tzu-Pin Lu Tzu-Pin Lu Mong-Hsun Tsai Mong-Hsun Tsai Li-Han Chen Liang-Chuan Lai Liang-Chuan Lai Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang
author_sort	Wentao Fang
title	Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas
title_short	Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas
title_full	Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas
title_fullStr	Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas
title_full_unstemmed	Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas
title_sort	novel tumor-specific antigens for immunotherapy identified from multi-omics profiling in thymic carcinomas
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/22f1c15fdbbf44fdba19a94394394d98
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Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas

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