未翻译区域 (UTR) 是个性化免疫疗法新抗原的潜在新来源
Christopher C T Sng1, Ashwin Adrian Kallor2, Benjamin S Simpson1
1Cancer Research UK Lung Cancer Centre of Excellence, University College London (UCL) Cancer Institute, London, United Kingdom.
Frontiers in immunology
|April 1, 2024
概括
来自非正规突变的未翻译区域 (UTR) 新抗原为癌症免疫治疗提供了一个新的标. 一种名为PrimeCUTR的新工具可以识别这些UTR新抗原,从而有可能改善个性化癌症治疗方法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 生物信息学是一种生物信息学.
背景情况:
- 新抗原在检查点抑制剂 (CPI) 治疗期间对抗瘤免疫是至关重要的.
- 未翻译区域 (UTR) 是免疫新抗原的未充分探索的来源.
- 准确的新抗原鉴定对于开发向癌症疗法至关重要.
研究的目的:
- 描述来自UTR的新抗原的情况.
- 开发和验证一个计算工具,PrimeCUTR,用于预测UTR新抗原.
- 评估UTR新抗原在CPI治疗反应中的潜力.
主要方法:
- 将PrimeCUTR工具应用于341名CPI治疗患者的全基因组测序数据.
- 分析了癌症免疫型数据集,以检测UTR新抗原的MHCI类呈现.
- 研究了UTR新抗原的频率,对自我蛋白质组不相似性的贡献,以及与CPI反应的关联.
主要成果:
- 在72.7%的患者中 (开始增益) 和19.3%的患者 (停止损失) 预测了UTR新抗原.
- UTR新抗原对具有高自我蛋白质差异性 (12.4%) 的新抗原有显著的贡献.
- 在黑色素瘤中确定了两种复发性UTR新抗原和两种MHCI类呈现UTR新抗原.
结论:
- PrimeCUTR增强了新抗原的发现,特别是那些与自我不同的人.
- UTR新抗原代表了个性化癌症治疗的有希望的途径.
- 需要进一步的研究来确认UTR新抗原的免疫性和临床实用性.
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