Chen Xiongfeng, Zhou Zhuan, Yazgan Zeynep, Xie Luyu, Rossi Francesca, Liu Yang, Zhang Bo, Polanco Patricio M, Zeh Herbert J, Kim Alex C, Huang Huocong
bioRxiv. 2024 Nov 17:2024.11.15.623232. doi: 10.1101/2024.11.15.623232.
Recent studies have identified a unique subtype of cancer-associated fibroblasts (CAFs) termed antigen-presenting CAFs (apCAFs), which remain the least understood CAF subtype. To gain a comprehensive understanding of the origin and function apCAFs, we construct a fibroblast molecular atlas across 14 types of solid tumors. Our integration study unexpectedly reveals two distinct apCAF lineages present in most cancer types: one associated with mesothelial-like cells and the other with fibrocytes. Using a high-resolution single-cell spatial imaging platform, we characterize the spatial niches of these apCAF lineages. We find that mesothelial-like apCAFs are located near cancer cells, while fibrocyte-like apCAFs are associated with tertiary lymphoid structures. Additionally, we discover that both apCAF lineages can up-regulate the secreted protein SPP1, which facilitates primary tumor formation and peritoneal metastasis. Taken together, this study offers an unprecedented resolution in analyzing apCAF lineages and their spatial niches.
最近的研究发现了一种独特的癌症相关成纤维细胞（CAF）亚型，称为抗原呈递CAF（apCAF），这仍然是人们了解最少的CAF亚型。为了全面了解apCAF的起源和功能，我们构建了一个涵盖14种实体瘤类型的成纤维细胞分子图谱。我们的整合研究意外地揭示了大多数癌症类型中存在两种不同的apCAF谱系：一种与间皮样细胞相关，另一种与纤维细胞相关。使用高分辨率单细胞空间成像平台，我们对这些apCAF谱系的空间生态位进行了表征。我们发现间皮样apCAF位于癌细胞附近，而纤维细胞样apCAF与三级淋巴结构相关。此外，我们发现两种apCAF谱系都可以上调分泌蛋白SPP1，这有助于原发性肿瘤形成和腹膜转移。综上所述，这项研究在分析apCAF谱系及其空间生态位方面提供了前所未有的分辨率。
