巨细胞的N-甘氨酸加工抑制了抗体依赖的细胞细胞分裂
Jesús S Aguilar Díaz de León1, Isaac Aguilar1, Adam W Barb1,2,3
1Department of Biochemistry and Molecular Biology, University of Georgia, 120 E. Green St, Athens, GA 30602, United States.
Glycobiology
|October 4, 2023
概括
处理N-甘氨酸调节巨细胞效应器的功能,增强抗体依赖的细胞化 (ADCP). 抑制这一过程可以促进巨细胞的活动,从而有可能优化抗体介导的抗癌疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 巨细胞是关键的髓状细胞,参与免疫反应,包括抗体依赖细胞化 (ADCP).
- 由Fc玛受体 (FcγRs) 介导的ADCP对于抗瘤抗体疗法至关重要,但也与免疫耐受性有关.
- 了解调节巨效应因子功能的因素是改善治疗策略的关键.
研究的目的:
- 为了研究阿斯巴拉金 (N) 相关的甘氨酸在调节原发性人类单细胞衍生的巨细胞功能中的作用.
- 为了确定抑制N-甘氨酸加工是否影响巨介导的ADCP.
主要方法:
- 初级人类单细胞分化为巨细胞.
- 巨被用N-甘氨酸加工抑制剂kifunensine进行治疗.
- 分析了向结合,抗体涂层细胞 (Rituximab涂层Raji B细胞,Trastuzumab涂层SKBR3细胞) 的ADCP,FcγR参与和免疫受体酸化.
主要成果:
- 基宁素治疗显著增强了巨细胞向结合和ADCP.
- 对B细胞和乳腺癌细胞系均观察到ADCP的增加.
- 抑制CD64/FcγRI最显著地降低了ADCP,其次是CD32/FcγRII和CD16/FcγRIII.
- 基宁素治疗增加了CD16抗体结合亲和力,并改变了Siglec-9,CD32a和LAIR-1等免疫受体的酸化.
结论:
- N-甘氨酸加工是巨细胞效应因子功能的关键调节者,包括ADCP.
- 抑制N-甘氨酸的处理增强了对抗体opsonized目标的巨介导的细胞分裂.
- 这些发现表明,准N-甘氨酸通路可能是优化抗体介导疗法的策略.
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