Th17类细胞和免疫抑制性巨细胞透到软组织肉瘤中具有明显成熟状态的三级淋巴体结构
Giulia Petroni1, Federico Scolari2, Guido Scoccianti3,4
1Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. giuliapetroni@gmail.com.
软组织肉瘤 (STS) 中的三级淋巴体结构 (TLS) 与更好的结果有关. 这项研究揭示了T助手17细胞和M2巨细胞在TLS形成中发挥关键作用,影响抗瘤免疫力和患者的生存.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 三级淋巴体结构 (TLSs) 与良好的预后相关,并在软组织肉瘤 (STSs) 中改善对免疫检查点抑制剂的反应.
- 由于稀有性和异质性,TLS形成的机制及其在STS中的抗瘤免疫力中的作用仍然不太清楚.
研究的目的:
- 调查STS中TLS的异质性,阐明驱动其形成和对抗瘤免疫的贡献的细胞机制.
- 确定特定的免疫细胞群和与TLS存在和STS患者生存相关的分子特征.
主要方法:
- 对31个未经治疗的STS标本进行了综合免疫组织化学和转录组分析.
- 使用5个公共数据集的外部批量,单细胞和空间转录组学数据进行验证.
- 对生殖中心 (GC) B细胞相关基因,T助手17 (Th17) 细胞特征和M2类巨标记物的分析.
主要成果:
- 在数量,局部,成熟和细胞组成方面,TLS表现出显著的异质性.
- 高GC B细胞基因表达与TLS存在有关,与Th17细胞特征相关,而低GC B细胞表达与免疫抑制M2类巨细胞相关.
- 具有高GCB细胞和Th17细胞特征,低M2类巨细胞的瘤显示出优异的生存结果.
结论:
- TLS是异质的,并且与STS的良好预后有关,B细胞是关键指标.
- 类似T辅助17类细胞和类似M2类巨细胞似乎在与STS相关的TLS形成和成熟中具有相反的作用.
- 这些发现为开发免疫治疗干预措施提供了基础,以增强STS中TLS介导的抗瘤免疫力.
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