在转移性癌症中,DUX4是免疫逃避和免疫治疗失败的常见驱动因素
Jose Mario Bello Pineda1,2,3,4, Robert K Bradley1,2,3
1Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
bioRxiv : the preprint server for biology
|July 28, 2023
概括
胚胎转录因子DUX4经常在转移性癌症中发现,阻碍免疫反应并降低免疫治疗的有效性. 向DUX4可能会改善晚期癌症患者的治疗结果.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 癌症免疫逃避是转移性疾病中免疫疗法失败的主要原因.
- 胚胎转录因子DUX4抑制干扰素γ信号传递和抗原呈现.
- 在一些原发性瘤中观察到异常的DUX4表达.
研究的目的:
- 调查转移性癌症中DUX4表达的流行率.
- 确定DUX4表达与免疫细胞透和免疫治疗反应的关联.
- 评估DUX4作为患者生存的预后生物标志物.
主要方法:
- 在各种转移性癌症类型中分析DUX4表达.
- 在瘤微环境中,DUX4水平与免疫细胞排除的相关性.
- 在尿路癌患者中对PD-L1阻断的客观反应率的评估.
- 生存分析包括DUX4表达,瘤突变负担和临床特征.
主要成果:
- DUX4表达在~10-50%的晚期膀,乳腺,脏,前列腺和皮肤癌中普遍存在.
- DUX4表达与免疫细胞排斥有显著的相关性.
- 在尿路癌中,DUX4与PD-L1阻塞的反应降低有关.
- DUX4表达独立地预测了较差的生存率,将中位数的生存率减少了一年多.
结论:
- DUX4是转移性癌症的常见特征,有助于免疫逃避.
- DUX4表达与免疫疗法耐药性和预后不佳有关.
- DUX4为克服免疫疗法耐药性的潜在生物标志物和治疗标.
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