CD8+ T细胞功能障碍的标志是在细胞分裂前与瘤抗原相遇的几个小时内建立起来的
Michael W Rudloff1, Paul Zumbo2,3, Natalie R Favret1
1Department of Medicine, Division of Hematology and Oncology, Department of Pathology, Microbiology, and Immunology, Vanderbilt School of Medicine, Nashville, TN, USA.
Nature immunology
|August 3, 2023
概括
瘤特异性CD8+T细胞 (TST) 快速失去功能,并早期表现出表观遗传变化,甚至在分裂之前. 这种早期的功能障碍,与感染不同,在癌症中打印出一种非功能状态.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- CD8+ T 细胞功能障碍或疲劳会损害抗癌免疫力.
- 据信,慢性抗原刺激会在几周内导致T细胞疲劳.
- 在激活数小时后的早期T细胞反应在癌症中仍然不太了解.
研究的目的:
- 研究早期CD8+T细胞分化,分裂和癌症中的表观遗传变化.
- 为了比较瘤携带小鼠和急性感染小鼠的早期T细胞反应.
- 了解T细胞功能障碍和表观遗传改造的时间表.
主要方法:
- 评估 CD8+ T 细胞功能,细胞分裂,染色质可访问性和转录.
- 利用了携带瘤的小鼠模型和急性感染的小鼠模型.
- 分析了T细胞激活后数小时内发生的早期细胞事件.
主要成果:
- 瘤特异性CD8+T细胞 (TST) 在细胞分裂之前表现出受损的效应器功能.
- 在瘤发育早期,TST获得了疲的表观遗传特征.
- 瘤暴露导致了渐进的表观遗传改造,固化功能障碍.
- 与感染相比,早期T细胞命运分歧发生在瘤中.
结论:
- 癌症中的CD8+T细胞功能障碍是一个快速的过程,发生在细胞分裂之前.
- 表观遗传印记有助于TST的早期和持续的功能障碍状态.
- 在癌症和急性感染背景下,T细胞耗尽的动力学显著不同.
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