血交换和辐射使免疫疗法耐药黑色素瘤重新敏感:一期I期试验
Jacob J Orme1,2, Henan Zhang3, Prashanth Lingamaneni4
1Department of Oncology, Mayo Clinic, Rochester, MN, USA. orme.jacob@mayo.edu.
Nature communications
|March 14, 2025
概括
治疗性血交换 (TPE) 在耐免疫检查点抑制剂 (ICI) 的晚期黑色素瘤患者中有效降低了可溶性PD-L1,改善了治疗反应. 这种方法可以克服其他癌症的ICI耐药性.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
背景情况:
- 免疫检查点抑制剂 (ICI) 在晚期黑色素瘤中显示出有效性,但耐药性很常见.
- 瘤衍生的可溶性PD-L1 (sPD-L1) 和其他免疫抑制因素有助于ICI耐药性.
- 治疗性血交换 (TPE) 是一种消除循环免疫抑制因素的潜在方法.
研究的目的:
- 评估TPE在降低ICI耐性黑色素瘤患者sPD-L1的安全性和有效性.
- 评估TPE对克服ICI耐药性和改善临床结果的影响.
- 探索sPD-L1的变化,其他免疫抑制因素,免疫细胞表型和患者存活率之间的相关性.
主要方法:
- 一项涉及18名患有转移性ICI耐药黑色素瘤和升高sPD-L1.1的患者的研究.
- 患者接受了对病变子集的放射治疗,TPE,并通过ICI重新挑战.
- 主要终点包括不良事件和sPD-L1减少;次要终点包括整体存活率,应答率和无进展存活率.
主要成果:
- 治疗耐受性良好,通过TPE显著降低sPD-L1水平 (平均78%,p < 0.0001).
- 总体响应率为61%,其中16.7%是完全响应和44.4%是部分响应.
- 减少sPD-L1和特异性免疫细胞变化预测了改善的整体存活率.
结论:
- TPE有效地减少循环中的sPD-L1和其他免疫抑制因素,可能使ICI耐受性黑色素瘤重新敏感.
- 持续升高或sPD-L1的快速反弹表明需要多次TPE课程来获得持续的益处.
- 这些发现可能会扩展到其他表现出ICI耐药性的癌症.
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