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

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

doi:10.3389/fimmu.2021.748820

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

Front Immunol. 2021 Nov 16:12:748820. doi: 10.3389/fimmu.2021.748820. eCollection 2021.

Authors

Wentao Fang¹, Chia-Hsin Wu², Qiang-Ling Sun^{1

3}, Zhi-Tao Gu¹, Lei Zhu⁴, Teng Mao¹, Xue-Fei Zhang¹, Ning Xu¹, Tzu-Pin Lu^{5

6}, Mong-Hsun Tsai^{5

7}, Li-Han Chen⁸, Liang-Chuan Lai^{5

9}, Eric Y Chuang^{2

5

10

11}

Affiliations

¹ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China.
² Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
³ Thoracic Cancer institute, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁵ Bioinformatics and Biostatistics Core, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
⁶ Department of Public Health, National Taiwan University, Taipei, Taiwan.
⁷ Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
⁸ Institute of Fisheries Science, National Taiwan University, Taipei, Taiwan.
⁹ Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹⁰ Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan.
¹¹ Master Program for Biomedical Engineering, China Medical University, Taichung, Taiwan.

Abstract

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.

Keywords: RNA sequencing (RNAseq); driver alteration; gene fusion; immune checkpoint inhibitor (ICI); immunotherapy; neoantigen; thymic carcinoma (TC); whole-exome sequencing (WES).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antigens, Neoplasm / immunology*
Carcinogenesis
Female
Genomics
Humans
Immunotherapy
Male
Middle Aged
Thymoma / genetics*
Thymoma / immunology*
Thymus Neoplasms / genetics*
Thymus Neoplasms / immunology*
Transcriptome

Substances

Antigens, Neoplasm