HIF调节多种翻译内源逆转录病毒:对癌症免疫疗法的影响
Qinqin Jiang1, David A Braun2, Karl R Clauser3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Cell
|March 1, 2025
概括
清细胞细胞癌 (ccRCC) 显示出由HIF诱导的内源逆转录病毒 (ERV) 引起的免疫性. 这些ERV产生T细胞反应,为ccRCC免疫治疗提供了新的途径.
科学领域:
- 癌症学
- 免疫学
- 遗传学
背景情况:
- 尽管突变率较低,但清细胞癌 (ccRCC) 具有免疫性.
- 在ccRCC中,VHL基因失活导致HIF转录因子上调.
- 之前的病例显示,在治愈的ccRCC患者中,捐赠者T细胞识别了ERV.
研究的目的:
- 研究HIF诱导的内源逆转录病毒 (ERV) 在ccRCC免疫性中的作用.
- 确定ERV是否可以在ccRCC中引起T细胞反应.
- 探索ERVs在癌症免疫治疗中的潜力.
主要方法:
- 在ccRCC瘤中分析ERV表达.
- 来自ERV的HLA结合的鉴定.
- 评估T细胞对ERV衍生的的反应.
- 在非ccRCC瘤中使用HIF稳定剂诱导ERV表达.
主要成果:
- 在ccRCC中,HIF会诱导多个ERV.
- 由HIF诱导的ERV转化为与HLA结合的.
- 这些可以产生抗原特异性T细胞反应.
- 在其他瘤中使用HIF稳定剂可以诱导ERV表达.
结论:
- 由HIF诱导的ERV是ccRCC特异性抗原的来源.
- 可以引起抗瘤T细胞免疫力.
- 在ccRCC免疫疗法开发中,ERVs是一个有前途的目标.
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