The apCAF orchestrates tertiary lymphoid structure formation in clear cell renal cell carcinoma via chemokine networks:a spatial multi-omics research
10.3969/j.issn.1009-8291.2025.11.006
- VernacularTitle:apCAF通过趋化因子网络驱动肾透明细胞癌三级淋巴结构形成的空间多组学研究
- Author:
Qintao GE
1
;
Wenhao XU
;
Wei ZHANG
;
Anwaier AIHETAIMUJIANG
;
Hailiang ZHANG
Author Information
1. 复旦大学附属华东医院泌尿外科,上海 200040;复旦大学附属肿瘤医院泌尿外科,上海 200032;复旦大学上海医学院肿瘤学系,上海 200032
- Publication Type:Journal Article
- Keywords:
clear cell renal carcinoma;
tertiary lymphoid structures;
cancer-associated fibroblast;
antigen-presentation carcinoma-associated fibroblast;
immunotherapy;
spatial transcriptomics analysis
- From:
Journal of Modern Urology
2025;30(11):938-946
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the heterogeneous lineage of cancer-associated fibroblast(CAF)in clear cell renal cell carcinoma(ccRCC),and explore the relationship between antigen-presentation carcinoma-associated fibroblast(apCAF)and the spatial distribution and formation potential of tertiary lymphoid structure(TLS).Methods Seven single-cell transcriptomic cohorts(n=88)were integrated,and batch effects were corrected using the Harmony algorithm to identify consistent CAF subpopulations across samples.The spatial transcriptomics(GSE175540,n=24)were combined to analyze the spatial interactions between CAF and TLS.Functional annotation was performed using AUCell,and Wilcoxon test was employed to compare the differences in CAF abundance between the immune-sensitive group and the resistant group.The co-localization of TLS with different chemokines was assessed.Results Nine conserved CAF clusters were defined,which were reproducible across different cohorts.Among them,Fibro 4 served as an antigen-presenting type of apCAF,characterized by high expression of HLA-DRA/CD74,and abundance in the immune-sensitive group;its functions were enriched in T cell activation pathways;it was strongly correlated with TLS,and positioned at the periphery of TLS.Cell co-localization analysis revealed that apCAF could recruit lymphocytes to aggregate and form TLS structures via the CXCL13-CXCR5 and CCL19-CCR7 axes.Conclusion This study first reveals that apCAF drives the formation of TLS in ccRCC through a chemokine network,thereby correlating with the response to immunotherapy.The apCAF-TLS axis provides a new strategy for targeting stromal remodeling in the immune microenvironment,and its combined scoring is expected to serve as a biomarker for predicting the efficacy of immune checkpoint blockade therapy.
