Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment

被引：0
作者：
Chenxi Ma
Chengzhe Yang
Ai Peng
Tianyong Sun
Xiaoli Ji
Jun Mi
Li Wei
Song Shen
Qiang Feng
机构：
[1] Cheeloo College of Medicine,Department of Human Microbiome and Periodontology and Implantology and Orthodontics, School and Hospital of Stomatology
[2] Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration and Shandong Provincial Clinical Research Center for Oral Diseases,Department of Oral and Max
[3] Qilu Hospital of Shandong University,Institute of Stomatology
[4] Shandong University,Department of Stomatology
[5] Central Hospital Affiliated to Shandong First Medical University,undefined
[6] State Key Laboratory of Microbial Technology,undefined
[7] Shandong University,undefined
来源：
Molecular Cancer | / 22卷
关键词：
Spatial transcriptomics; Single-cell RNA sequencing; Pan-cancer analysis; Cancer-associated fibroblasts; Tumor microenvironment; Tumor immunotherapy;
D O I：
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学科分类号：
摘要：
Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays a crucial role in remodeling the tumor microenvironment (TME). Here, through the integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups of CAFs and described their spatial distribution characteristics. Additionally, the analysis of single-cell RNA sequencing (scRNA-seq) data from three additional common cancer types and two newly generated scRNA-seq datasets of rare cancer types, namely epithelial-myoepithelial carcinoma (EMC) and mucoepidermoid carcinoma (MEC), expanded our understanding of CAF heterogeneity. Cell–cell interaction analysis conducted within the spatial context highlighted the pivotal roles of matrix CAFs (mCAFs) in tumor angiogenesis and inflammatory CAFs (iCAFs) in shaping the immunosuppressive microenvironment. In patients with breast cancer (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity in facilitating cancer cell proliferation, promoting epithelial-mesenchymal transition (EMT), and contributing to the establishment of an immunosuppressive microenvironment. Furthermore, a scoring system based on iCAFs showed a significant correlation with immune therapy response in melanoma patients. Lastly, we provided a web interface (https://chenxisd.shinyapps.io/pancaf/) for the research community to investigate CAFs in the context of pan-cancer.
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