由三阴性乳腺癌细胞分泌的加勒-3调节T细胞功能
Annat Raiter1, Yael Barhum2, Julia Lipovetsky3
1Felsenstein Medical Research Center, Beilinson Campus, Petah Tikva, Israel; Tel Aviv University, Faculty of Medicine and Health Sciences, Tel Aviv, Israel; Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
概括
三重阴性乳腺癌细胞分泌加勒-3 (Gal-3) 抑制T细胞功能,增加免疫抑制. 准Gal-3可能为治疗这种侵袭性癌症提供新的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 三重阴性乳腺癌 (TNBC) 是具有攻击性的,对化疗免疫疗法的反应是可变的.
- 了解TNBC瘤微环境对于开发新的免疫向剂至关重要.
- 由TNBC细胞分泌的加勒-3 (Gal-3) 曾经被证明可以通过抑制T细胞中的CD45信号来诱导免疫抑制.
研究的目的:
- 研究TNBC中分泌的Gal-3和T细胞之间的相互作用.
- 阐明Gal-3影响瘤免疫微环境的机制.
- 为了确定TNBC的潜在治疗点.
主要方法:
- 通过CRISPR/Cas9基因编辑,创建Gal-3负 (Gal-3neg) TNBC细胞系.
- 在体外共培养Gal-3neg TNBC细胞与外周血液单核细胞 (PBMCs).
- 使用植入Gal-3阳性 (Gal-3pos) 和Gal-3阴性TNBC瘤的小鼠进行体内研究.
- 从TNBC患者和体外模型中对T细胞的RNA测序.
- 对T细胞种群的分析,包括调控性T细胞 (Tregs) 和耗尽的T细胞.
主要成果:
- 与Gal-3pos瘤相比,Gal-3neg瘤在PBMC接种后在小鼠中显示出增长减缓.
- 尽管PBMC接种了疫苗,但Gal-3pos瘤继续增长,Treg透率增加.
- 来自高Gal-3水平的TNBC患者的T细胞显示氧化酸化基因表达减少.
- 在体外,Gal-3pos TNBCs导致线粒体功能障碍,CD8 T 细胞中的活性氧物种增加,以及耗尽的 T 细胞的增加.
结论:
- 由TNBC细胞分泌的Gal-3通过调节CD4 T调节细胞和CD8 T耗尽细胞来促进免疫抑制.
- -3对T细胞功能产生负面影响,特别是氧化酸化和线粒体活性.
- 针对Gal-3介导的免疫抑制途径为TNBC提供了潜在的治疗策略.
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