在CTLA-4依赖反回路中断时,与瘤相关的Treg细胞的扩张
Francesco Marangoni1, Ademi Zhakyp2, Michela Corsini3
1The Center for Immunology and Inflammatory Diseases (CIID), Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Institute for Immunology, University of California, Irvine, Irvine, CA 92697, USA.
Cell
|June 22, 2021
概括
通过与树突细胞 (cDC) 相互作用,Foxp3+ T调节细胞控制瘤耐受性. Treg细胞使用CTLA-4来限制自身的激活,这一过程对瘤排斥至关重要.
科学领域:
- 免疫学
- 癌症生物学
- 细胞相互作用
背景情况:
- 在瘤微环境 (TME) 中,Foxp3+ T调节细胞对维持免疫耐受性至关重要.
- 在TME中调节Treg细胞功能和激活的精确机制尚未完全理解.
研究的目的:
- 在TME中研究控制Treg细胞激活和功能的细胞相互作用.
- 阐明控制瘤Treg细胞数量和活动的调节反循环.
主要方法:
- 使用内显微镜可视化和实时分析TME中的细胞相互作用.
- 通过与瘤相关的常规树突细胞 (cDC) 呈现的Treg细胞识别的特征.
- 评估CTLA-4和CD28在Treg细胞调节和增殖中的作用.
主要成果:
- 在TME中,Treg细胞优先识别cDCs所呈现的抗原.
- 与cDC的不稳定相互作用维持Treg细胞功能,而稳定的相互作用激活T辅助细胞.
- Treg细胞利用CTLA-4降低cDCs上的共刺激分子,限制它们自身的激活.
- CTLA- 4 阻断导致Treg 细胞的过度增殖,需要Treg 细胞的失活来排斥瘤.
结论:
- 通过CTLA-4和CD28依赖的反循环,Treg细胞在TME中自我调节其群体大小.
- 通过CTLA-4阻断破坏这种Treg细胞调节循环可能会抵消癌症治疗的疗效.
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