在微卫星不稳定的瘤中共享免疫多位基因突变
Vladimir Roudko1, Cansu Cimen Bozkus1, Theofano Orfanelli2
1Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
Cell
|December 1, 2020
概括
高微卫星不稳定性 (MSI-H) 瘤具有编码免疫新抗原的共享框架转移突变. 这些发现支持为MSI-H和林奇综合征患者开发"现成"癌症疫苗.
科学领域:
- 癌症学
- 免疫学
- 遗传学
背景情况:
- 微卫星不稳定性高 (MSI-H) 的瘤具有很高的突变率,并且对免疫治疗有很好的反应.
- 框架转移突变在MSI-H癌症中很常见,导致新瘤抗原的产生.
研究的目的:
- 在MSI-H癌症中识别共享的移突变及其编码表位.
- 评估这些新抗原的免疫性和癌症疫苗开发潜力.
主要方法:
- 对MSI-H子宫内膜癌,结直肠癌和胃癌的内基突变进行分析.
- 预测表位素与常见的MHC等位基结合.
- 使用外周血液单核细胞进行T细胞刺激实验.
主要成果:
- 在不同MSI-H癌症类型中识别了编码多个表位的共享框架转移突变.
- 这些表位表现出高种群发生率,广泛的瘤亚克隆存在,并预测与频繁的MHC等位基因结合.
- 框架转移衍生的新抗原与自我/病毒抗原不同,并且在体外显示出确定的免疫性.
结论:
- 在MSI-H和林奇综合征患者中,来自共享的框架转移突变的瘤特异性抗原广泛存在,并且具有高度免疫性.
- 这些发现为设计常见的,现成的癌症疫苗提供了有前途的途径.
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