在成功的免疫检查点癌症治疗过程中,高维度分析描绘了髓状和淋巴状区的重塑
Matthew M Gubin1, Ekaterina Esaulova2, Jeffrey P Ward3
1Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
免疫检查点疗法 (ICT) 重塑瘤微环境,影响像单细胞和巨细胞这样的骨髓细胞. 这项研究揭示了ICT影响早期巨细胞, 不仅仅是成熟的巨细胞,
科学领域:
- 免疫学
- 癌症学
- 细胞生物学
背景情况:
- 免疫检查点治疗 (ICT) 主要针对淋巴细胞,但广泛影响瘤微环境.
- 了解ICT对所有免疫细胞类型的综合影响对于优化癌症治疗至关重要.
研究的目的:
- 在未经限制的生长和有效的ICT过程中,在同源性小鼠瘤中定义所有造血细胞群的变化.
- 在ICT下研究骨髓细胞区的动态变化,特别是单细胞和巨细胞.
主要方法:
- 使用单细胞RNA测序 (scRNA-seq) 进行瘤透细胞的无偏基因表达分析.
- 使用质量细胞计量 (CyTOF) 进行细胞蛋白表达的纵向评估.
- 通过标记物CD206,CX3CR1,CD1d和iNOS定义的特定单细胞/巨细胞亚群的分析变化.
主要成果:
- 在ICT过程中观察到淋巴状和骨髓状内区的显著重塑.
- 鉴定出在ICT过程中动态变化的单细胞/巨细胞的不同亚群,部分依赖干扰素- (IFNγ).
- 证据表明ICT影响循环单细胞和早期透的巨细胞,影响它们的两极化/激活.
结论:
- 在瘤微环境中诱导髓状细胞群的实质性变化.
- 在ICT期间的巨分化似乎是由进入瘤的前体细胞的影响驱动的.
- 这些发现为ICT的机制提供了洞察力,并提出了增强治疗功效的潜在目标.
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