间质细胞
癌症研究
免疫系统
肿瘤微环境
质量细胞仪
生物
血管生成
医学
表型
免疫学
基因
生物化学
作者
Haiyang Zhou,Yiwen Shen,Guangyong Zheng,Beibei Zhang,Anqi Wang,Jing Zhang,Hao Hu,Jiayi Lin,Sanhong Liu,Xin Luan,Weidong Zhang
摘要
Abstract Background Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in‐depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies. Methods We integrated single‐cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three‐dimensional bioprinting technique, canonical ex vivo co‐culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME. Results This study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7 + / THBS1 + myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte‐mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A + macrophages that exhibit M2‐phenotype were enriched in the tumoral niche and high expression of MS4A4A + was associated with poor prognosis in the cohort data. The ligand‐receptor‐based intercellular communication analysis revealed the tight interaction of MUC1 + malignant cells and ZEB1 + endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications. Conclusions Our study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA. Key points Tumour microenvironment profiling of MCA is developed. MUC1 + tumour cells interplay with FGF7 + / THBS1 + myofibroblasts to promote MCA development. MS4A4A + macrophages exhibit M2 phenotype in MCA. ZEB1 + endotheliocytes engage in EndMT process in MCA.
科研通智能强力驱动
Strongly Powered by AbleSci AI