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单细胞和空间转录组分析揭示了与瘤进展和在鼻癌中免疫治疗反应相关的三级淋巴体结构

Yang Liu¹, Shuang-Yan Ye², Shuai He¹

¹State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.

Nature communications

|September 4, 2024

概括

三级淋巴体结构通过成熟的血细胞来增强癌症免疫疗法,这些细胞向瘤细胞. 这些结构富含特定的免疫细胞,与癌症的更好的预后和治疗反应相关.

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 (TLS) 是与癌症结果相关的免疫细胞聚合物.
TLS和瘤细胞聚合物之间的精确相互作用在很大程度上仍未定义.

研究的目的:

阐明鼻癌中TLS内的细胞组成和相互作用.
了解TLS组件在瘤细胞聚合物和免疫治疗反应方面的功能作用.

主要方法:

从77个活检和血液样本中分析了343829个细胞的单细胞转录组.
来自15个鼻瘤的31,316个斑点的空间分辨率转录.
确定关键细胞种群及其在TLS内的空间分布.

主要成果:

确定了关键的TLS群体:与癌症相关的CXCL13+纤维细胞,干状CXCL13+CD8+T细胞以及B和T毛囊辅助细胞.
生殖中心反应成熟的血细胞透到瘤集群中,促进恶性细胞亡并增强免疫疗法.
CXCL13+ 纤维细胞支持 B 细胞激活和抗体产生,同时激活在瘤集群中耗尽的 CD8+ T 细胞.

结论:

TLS组件及其相互作用对于抗瘤免疫力和免疫疗法的有效性至关重要.
与TLS相关的细胞特征预测患者的预后和对PD-1阻断疗法的反应.
了解TLS为增强癌症治疗提供了潜在的治疗策略.

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