LILRB3 支持髓状细胞的免疫抑制活动和瘤发育
Ryan Huang1, Xiaoye Liu1, Jaehyup Kim2
1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas.
Cancer immunology research
|December 19, 2023
概括
在免疫抑制性髓状细胞上阻断白细胞Ig类受体亚家族B3 (LILRB3) 抑制癌症生长. 这种新的方法显示了通过激活免疫系统来实现固体瘤免疫治疗的希望.
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:
- 针对T细胞的免疫疗法在癌症治疗中表现出有限的成功.
- 免疫抑制性髓状细胞,包括髓状细胞衍生抑制细胞 (MDSC),阻碍抗瘤免疫力,促进瘤进展.
- 白细胞Ig类受体亚家族B3 (LILRB3) 是髓状细胞上的抑制受体,但其在癌症免疫力中的作用尚不清楚.
研究的目的:
- 调查LILRB3是否是免疫抑制性髓状细胞的关键检查点.
- 为了确定阻断LILRB3信号是否可以激活免疫系统对抗固体瘤.
- 探索LILRB3作为癌症免疫治疗中的潜在治疗标.
主要方法:
- 研究了LILRB3通过 galectin-4和galectin-7的激活.
- 在固体癌症患者的免疫抑制性髓状细胞上证实了LILRB3的功能表达.
- 利用对抗性抗体阻断患者样本中的LILRB3信号传递和骨髓特异性LILRB3转基因小鼠.
- 评估瘤发育和T细胞依赖的免疫反应.
主要成果:
- 发现加勒-4和加勒-7可诱导LILRB3的激活.
- 在功能上,LILRB3 在免疫抑制性髓状细胞上得到表达.
- 在人类癌症样本中,LILRB3阻断抑制了免疫抑制性髓状细胞活性.
- 抗LILRB3治疗通过依赖T细胞的机制阻碍了小鼠的瘤发育.
结论:
- LILRB3在调节免疫抑制性髓状细胞方面发挥着关键作用.
- 阻止LILRB3信号传递代表了固体癌症免疫治疗的潜在新策略.
- 向LILRB3可以通过重新激活抗瘤免疫力来克服当前免疫治疗的局限性.
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