Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China.
Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Front Immunol. 2021 Nov 16;12:748820. doi: 10.3389/fimmu.2021.748820. eCollection 2021.
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 and frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the - 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.
胸腺癌（TC）是最具侵袭性的胸内上皮肿瘤。微卫星不稳定、全基因组加倍或基因融合产生的其他肿瘤特异性抗原的 TC 患者最有可能受益于免疫治疗。然而，由于这种疾病的罕见性，如何确定潜在的生物标志物以及什么构成最佳治疗方案在很大程度上仍不清楚。因此，我们整合了 TC 患者的基因组和转录组分析，结果表明和 中的移码缺失经常产生新抗原。此外，在受影响的患者中预测到了中位数为 3 个融合衍生的新抗原，特别是在 TC 患者中反复预测到的 - 新抗原。最后，发现了具有早期证据水平的潜在可操作改变，可用于设计临床试验。总之，这项研究阐明了我们对肿瘤发生的理解，并为 TC 的分子特征分析和免疫治疗提供了新途径。
