抑制DNMT和HDAC会诱导来自人类内源性逆转录病毒元素衍生转录的免疫新抗原
Ashish Goyal1, Jens Bauer2,3,4, Joschka Hey1,5,6
1Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nature communications
|October 23, 2023
概括
表观遗传疗法可以通过激活内源逆转录病毒元素 (ERVs) 来增强癌症免疫疗法. 这项研究确定了新的ERV衍生的新抗原,显示了它们在患者中触发抗癌T细胞反应的潜力.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 针对新抗原的癌症免疫疗法已经改变了癌症治疗.
- 表观遗传疗法可能通过重新激活内源逆转录病毒元素 (ERVs) 与免疫疗法协同作用.
研究的目的:
- 研究表观遗传药物诱导ERVs的新抗原的潜力.
- 为了识别和验证治疗诱导的新抗原用于癌症治疗.
主要方法:
- 用DNA甲基转移酶抑制剂 (DNMTi) 和/或希斯脱乙酶抑制剂 (HDACi) 治疗的癌症细胞系的深度RNA测序.
- 新型转录组组装以识别ERV衍生的新型多基化转录 (TINPATs).
- 免疫类药物检测人类白细胞抗原 (HLA) 呈现的新抗原 (t-新).
主要成果:
- 在表观遗传治疗后,确定了数千种源自ERV的TINPAT.
- 检测到来自TINPATs的45种光谱验证的t-新.
- 在Decitabine治疗后的急性髓性白血病 (AML) 患者样本中证实了t-新.
结论:
- 表观遗传疗法可以产生ERV衍生的新抗原,可能引起抗癌T细胞反应.
- 这些发现支持ERV衍生的新抗原在癌症治疗的综合表观遗传和免疫疗法中使用.
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