让保护性瘤微环境对抗体介导疗法的敏感化
Christian P Pallasch1, Ilya Leskov2, Christian J Braun2
1Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Internal Medicine, Center of Integrated Oncology, University of Cologne, Cologne 50931, Germany.
化疗可以通过改变瘤微环境来增强抗体治疗. 环胺诱导细胞因子促进巨细胞活动,提高免疫系统消除白血病细胞的能力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 耐治疗的微环境对治疗扩散性癌症构成了重大挑战.
- 基于抗体的疗法可能由于瘤微环境介导的耐药性而无效.
研究的目的:
- 研究B细胞白血病中抗体治疗耐药性的机制.
- 通过调节瘤微环境来识别克服治疗抵抗的策略.
主要方法:
- 利用一种治疗不耐用的B细胞白血病的人性化模型.
- 治疗抗体和环胺的联合治疗方案.
- 分析了骨髓瘤微环境和巨细胞活动中的变化.
主要成果:
- 白血病细胞透到骨髓中会产生一种耐药的微环境,阻碍抗体介导清除.
- 环胺诱导瘤细胞中的急性分泌激活表型 (ASAP),释放细胞因子 (CCL4,IL8,VEGF,TNFα).
- 这些释放的细胞因子促进了巨细胞的透,并增强了骨髓中的细胞活动.
结论:
- 结合化学免疫疗法,特别是使用环胺和治疗抗体,可以克服耐药性.
- 诱导与压力相关的细胞因子可以有效地利用先天免疫系统去除癌细胞.
- 这种策略提供了一种强有力的方法,通过改变瘤微环境来增强向治疗方法.
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