探索TGF-β通路活性和对转移性黑色素瘤患者检查点抑制的反应之间的关系
Stefan G van Ravensteijn1, Avital L Amir2, Daniele V F Tauriello3,4
1Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
Clinical and experimental immunology
|December 12, 2024
概括
免疫检查点抑制 (ICI) 是一种黑色素瘤治疗方法,但会发生耐药性. TGF-β途径没有预测耐药性,但刺途径确实如此,表明其作为ICI反应和晚期黑色素瘤生存的生物标志物的潜力.
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:
- 免疫检查点抑制 (ICI) 提供了有效的黑色素瘤治疗.
- 对ICI的内在耐药性影响了一小部分患者.
- 转化生长因子-β (TGF-β) 途径活性与免疫逃脱和ICI耐药性有关.
研究的目的:
- 调查TGF-β通路活性与晚期黑色素瘤中对ICI的耐药性之间的联系.
- 分析其他信号通路活动在ICI耐药性中的作用.
- 为了确定预测ICI治疗结果的潜在生物标志物.
主要方法:
- 在34名晚期黑色素瘤患者的瘤组织中分析了8个信号通路 (包括TGF-β和Hedgehog) 的活性.
- 评估途径活动得分 (PAS) 对于与生存和ICI反应的关联.
- 使用化SMAD2 (pSMAD2) 水平作为TGF-β通路激活的独立测量.
主要成果:
- 在TGF-β通路活性 (PAS或pSMAD2) 和ICI治疗反应或无进展生存率之间没有发现显著的关联.
- 与非响应者相比,响应者中的刺路径活动得分明显较低 (P=0.038).
- 高刺PAS被确定为ICI耐药性的重要预测因子 (OR 0.88,P=0.033) 和更差的无进展生存率 (HR 1-1.1,P=0.012).
结论:
- 在接受ICI的晚期黑色素瘤患者中,TGF-β通路的激活与治疗反应或生存没有显著的关系.
- 刺通路活动显示出作为ICI治疗反应和患者存活率的预测生物标志物的潜力.
- 对子通路作用的进一步研究可能会导致改善黑色素瘤的治疗策略.
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