瘤特异性激活叶酸受体β可使免疫细胞在瘤微环境中的重编程
Fenghua Zhang1, Bo Huang1, Sagar M Utturkar2
1Department of Chemistry and Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States.
Frontiers in immunology
|February 22, 2024
概括
叶酸受体β (FRβ) 在瘤中变得活跃,使得针对性地向免疫抑制性髓状细胞提供治疗. 这种方法重聚瘤免疫力,抑制瘤生长,没有全身毒性.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
背景情况:
- 叶酸受体 (FRs) 有不同的细胞功能.
- 叶酸受体 (FRβ) 的β异型是免疫抑制性髓状细胞的生物标志物,但其功能尚不清楚.
研究的目的:
- 描述FRβ在免疫抑制性巨细胞中的功能.
- 通过利用瘤诱导的FRβ激活来开发固体瘤的向治疗方法.
主要方法:
- 巨细胞与细胞因子和癌细胞介质的化.
- 针对性地向瘤透的FRβ.传递一个类似收费的受体7激动剂.
- 单细胞RNA测序以分析基因表达变化.
- 评估瘤生长抑制和全身毒性.
主要成果:
- 在暴露于抗炎症条件或瘤微环境的巨细胞中,FRβ结合叶酸.
- 瘤透的FRβ可以被功能激活以向免疫抑制性髓状细胞.
- 向疗法重新极化了与瘤相关的巨细胞,并诱导了其他免疫细胞的炎症转移,抑制了瘤的生长.
- 治疗没有显示出系统性毒性.
结论:
- 在瘤微环境中的FRβ激活提供了一个新的治疗策略.
- 瘤髓状细胞的有针对性的重编程可以逆转免疫抑制并抑制瘤生长.
- 这种方法代表了调节瘤微环境的潜在安全方法.
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