在抗PD-1治疗的TAP1缺陷黑色素瘤中,PMN-MDSCs负责免疫抑制
Xiao Zhang1, Kaijun Sun2, Bingzheng Zhong1
1Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510013, Guangdong, China.
概括
准多态核核髓衍生的抑制细胞 (PMN-MDSCs) 可以逆转TAP1缺陷瘤中的免疫抑制. 消除PMN-MDSC增强了抗瘤免疫力,在免疫治疗期间为这些癌症提供了潜在的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 与抗原处理 (TAP) 相关的载体对于HLA I抗原呈现至关重要.
- 低调TAP1与瘤进展和瘤微环境中的髓质衍生抑制细胞 (MDSC) 的增加有关.
- 尚不完全了解MDSCs对TAP1缺乏瘤免疫细胞耗尽的影响.
研究的目的:
- 研究MDSCs在TAP1缺陷瘤的免疫微环境中的作用.
- 确定是否准PMN-MDSCs可以改变免疫抑制并增强抗瘤免疫力.
- 评估PMN-MDSC枯竭作为TAP1缺乏瘤在免疫检查点阻塞 (ICB) 治疗中的治疗策略的潜力.
主要方法:
- 已建立的TAP1缺陷黑色素瘤的小鼠模型.
- 使用抗Ly6G抗体来耗尽多态核核髓衍生抑制细胞 (PMN-MDSCs).
- 通过流细胞计,定量PCR和免疫组织化学分析了免疫细胞透,细胞因子水平 (TNF-α,IL-6,TGF-β) 和免疫细胞功能.
主要成果:
- TAP1缺乏与增加的Ly6G+细胞透相关.
- 减少PMN-MDSC逆转了免疫抑制,增加了CD8+ T细胞和CD8+/Treg比率,但没有影响先天免疫细胞.
- 衰竭导致TNF-α和IL-6的升高,TGF-β的降低,表明活性抗瘤免疫反应.
结论:
- 在TAP1淘汰赛瘤中,PMN-MDSCs对于建立瘤原生免疫微环境至关重要.
- 针对PMN-MDSCs是TAP1缺乏瘤的有希望的治疗方法,特别是在ICB治疗期间.
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