特定于KSHV和HIV的T细胞迁移到卡波西肉瘤瘤中,并随着时间的推移而持续存在
Shashidhar Ravishankar1, Andrea M H Towlerton1,2, Iyabode L Tiamiyu1,3
1Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America.
bioRxiv : the preprint server for biology
|February 19, 2024
概括
免疫细胞,包括向卡波西肉瘤相关性疹病毒 (KSHV) 和艾滋病毒的T细胞,在卡波西肉瘤瘤中发现. 这些T细胞表现出对病毒抗原的高度识别,这表明免疫治疗的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 在瘤学瘤学.
背景情况:
- 卡波西肉瘤相关的疹病毒 (KSHV) 导致卡波西肉瘤 (KS),这是全球的一个重大健康问题,特别是在撒哈拉以南非洲的HIV阳性个体中.
- 撒哈拉以南非洲地区高KSHV血清流行率强调了了解KS病原和免疫反应的必要性.
研究的目的:
- 为了研究KS瘤内的免疫细胞组成和T细胞受体 (TCR) 谱.
- 在KS瘤微环境中识别和表征KSHV和/或HIV特有的T细胞.
主要方法:
- 在144个乌干达成年KS瘤活检中进行了转录分析和TCR谱系分析.
- 从9名成年人血液中单细胞RNA测序,以捕获和分析KSHV/HIV特异性T细胞.
- 工程T细胞表达已识别的TCR用于功能验证.
主要成果:
- CD8+ T细胞和M2极化巨细胞是KS瘤中占主导地位的免疫细胞.
- 在同一个人的不同瘤中观察到共享的TCR曲目.
- 在KS瘤中,大约25%的T细胞对KSHV或HIV抗原具有预测的特异性.
- 特定于KSHV/HIV的T细胞表现出一种抗原经验的效应因子表型和高敏度的病毒抗原在体外识别.
结论:
- 一种针对KSHV和HIV的多特异性,高敏度的T细胞反应局部化到KS瘤.
- M2巨细胞可能会抑制这种抗瘤T细胞反应.
- 了解这些T细胞反应,可以了解KS病变的发生和潜在的基于免疫的治疗策略.
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