State 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.
The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, P. R. China.
Nat Commun. 2024 Sep 4;15(1):7713. doi: 10.1038/s41467-024-52153-4.
Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13 cancer-associated fibroblasts, stem-like CXCL13CD8 T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13 cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13CD8 T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.
三级淋巴结构是与癌症结局相关的免疫细胞聚集物，但它们与肿瘤细胞聚集物的相互作用尚不清楚。在这里，我们使用鼻咽癌作为模型，分析了来自 77 个活检和血液样本的 343829 个细胞的单细胞转录组和来自 15 个肿瘤的 31316 个点的空间分辨转录组，以破译它们的组成成分及其与肿瘤细胞聚集物的相互作用。我们鉴定了三级淋巴结构中的重要细胞群体，包括 CXCL13 癌相关成纤维细胞、具有干细胞样特性的 CXCL13+CD8 T 细胞以及 B 和 T 滤泡辅助细胞。我们的研究表明，生发中心反应使浆细胞成熟。这些浆细胞与肿瘤细胞聚集物交错存在，促进 EBV 相关恶性细胞的凋亡，并增强免疫治疗反应。CXCL13 癌相关成纤维细胞促进 B 细胞黏附与抗体产生，激活 CXCL13+CD8 T 细胞，使其在肿瘤细胞聚集物中耗竭。与三级淋巴结构相关的细胞特征与预后和 PD-1 阻断反应相关，为癌症的治疗策略提供了新的见解。
