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免疫抑制性血细胞阻碍了T细胞依赖的免疫性化疗
Shabnam Shalapour1, Joan Font-Burgada1, Giuseppe Di Caro1
11] Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego (UCSD), 9500 Gilman Drive, San Diego, California 92093, USA [2] Department of Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, San Diego, California 92093, USA.
Nature
|April 30, 2015
概括
在前列腺癌中,B细胞促进化疗耐药性. 消除特定的免疫抑制性B细胞增强了抗瘤免疫反应,使得使用牛酸化疗有效治疗.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 瘤抗原会激活CD8(+) 细胞毒性T淋巴细胞 (CTLs),但已建立的瘤会产生免疫耐受性.
- 克服耐受性的疗法激活了瘤定向的CTLs,在一些人类癌症中显示出有效性.
- 化疗可以通过免疫细胞死亡刺激抗癌免疫反应.
研究的目的:
- 调查B细胞参与割抗性前列腺癌 (CRPC) 中的化疗耐药性.
- 确定B细胞在调节免疫性化疗剂oxaliplatin反应中的作用.
- 确定有助于免疫抑制和治疗耐药性的特定B细胞种群.
主要方法:
- 使用了三只小鼠前列腺癌模型.
- 研究了B细胞枯竭 (遗传或药理) 对氧沙治疗反应的影响.
- 通过其表面标记物和细胞因子生产 (IgA,IL-10,PD-L1) 来表征免疫抑制性B细胞.
主要成果:
- 在小鼠前列腺癌模型中,除非B细胞耗尽,否则oxaliplatin是耐火的.
- 低剂量牛酸通过诱导免疫细胞死亡来促进瘤导向的CTL激活,但这是由B细胞抑制的.
- 特定的免疫抑制性B细胞表达IgA,IL-10和PD-L1,依赖于TGFβ受体信号传递,被确定为抗性至关重要.
- 消除这些B细胞允许CTL依赖的瘤根除在oxaliplatin治疗的小鼠.
结论:
- B细胞,特别是IgA+,IL-10+,PD-L1+等离子体,是前列腺癌中化疗耐药性的关键调解者.
- 准这些免疫抑制性B细胞可以恢复对氧沙的敏感性,并增强CTL介导的瘤根除.
- 这些发现强调了一种新的治疗策略,用于克服侵袭性前列腺癌的抗性.
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