Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas
| Autor: | 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 |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Thymoma Carcinogenesis medicine.medical_treatment Immunology RNA sequencing (RNAseq) Disease Biology medicine.disease_cause Frameshift mutation Transcriptome Fusion gene Antigens Neoplasm medicine Humans thymic carcinoma (TC) Immunology and Allergy Thymic carcinoma Aged Original Research immune checkpoint inhibitor (ICI) whole-exome sequencing (WES) gene fusion Microsatellite instability Genomics Thymus Neoplasms Immunotherapy RC581-607 Middle Aged driver alteration medicine.disease neoantigen Cancer research Female immunotherapy Immunologic diseases. Allergy |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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