癌细胞可塑性定义了皮肤状细胞癌症免疫治疗的反应
Laura Lorenzo-Sanz1, Marta Lopez-Cerda2, Victoria da Silva-Diz2,3
1Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908, L'Hospitalet de Llobregat, Barcelona, Spain. llorenzo@idibell.cat.
Nature communications
|June 24, 2024
概括
皮肤状细胞癌 (cSCC) 的癌细胞根据其上皮或介质细胞特征改变其免疫逃避策略. 结合抗PD-L1和抗TIGIT疗法,可以通过向这些不同的免疫检查点来治疗cSCC.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 免疫检查点阻塞 (ICB) 已经改变了癌症治疗,但耐药性仍然是一个挑战,特别是在皮肤状细胞癌 (cSCC) 中.
- 了解cSCC免疫逃避机制对于改善治疗疗效至关重要.
研究的目的:
- 调查cSCC细胞上皮质/介质质可塑性如何影响免疫检查点 (IC) 连接体表达和免疫逃避.
- 为了确定IC通路在上皮细胞和介质细胞cSCC细胞中的差异性作用.
- 确定基于细胞可塑性的cSCC有效的ICB策略.
主要方法:
- 在小鼠模型中对表皮和介质细胞cSCC细胞中的免疫检查点连接体配置文件的分析.
- 评估表皮/介质细胞特征对免疫逃避路径的影响 (PD-1/PD-L1,CTLA-4/CD80,TIGIT/CD155).
- 在cSCC模型中对ICB组合疗法 (抗PD-L1/TIGIT) 的评估.
- 蛋白质表达 (E-cadherin,Vimentin,CD80,CD155) 与患者样本 (cSCC,HNSCC,黑色素瘤) 中的ICB反应的相关性.
主要成果:
- cSCC细胞表现出上皮/介质细胞的可塑性,改变了它们的IC联体体表达.
- 表皮细胞主要使用PD-1/PD-L1通路,而介质细胞利用CTLA-4/CD80和TIGIT/CD155进行免疫逃避.
- 与抗PD-L1和抗TIGIT的联合治疗对具有混合上皮和介质细胞成分的cSCCs最有效.
- 特定蛋白质 (E-cadherin,Vimentin,CD80,CD155) 的表达预测了人类癌症中对抗PD-1/PD-L1疗法的反应.
结论:
- 癌细胞的表皮/介质细胞状态决定了它们的免疫逃避机制和对ICB的反应.
- 同时针对PD-1/PD-L1和TIGIT/CD155通路,为cSCC提供了一个有前途的治疗策略.
- 基于表皮/介质细胞标记物的患者分层可以优化ICB治疗选择各种癌症.
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