Late Breaking Abstract - Mulberry-like cell clusters contained multi-types cells in MPE Promote malignant activities and Targeted intervention

The cell clusters exited in malignant pleural effusion (MPE). However, it remains elusive what cell types are present in these clusters. Exploring the cell types of cell cluster in MPE can determine whether the cell cluster can become a new model for the study of tumor microenvironment. Here by using scRNA-seq, we demonstrate that the cell clusters in MPE are composed of epithelial cells (mostly tumor cells), macrophages, fibroblasts, and other immune cells, and exhibit mulberry-like morphology. We revealed that the number of these cell clusters were negatively correlated with patient prognosis. Pathway enrichment analysis reveals that tumor cells within mulberry cell clusters were enriched in genes associated with the actin skeleton. Furthermore, a-SMA is a very important molecule in the cytoskeleton, we found a-SMA-high cells exhibited stronger invasion, migration and stemness than a-SMA-low. Mechanistically, cell clustering results in the reduction in Claudin-7 expression in tumor cells, which promotes the activation of the notch pathway, thereby upregulating the expression of a-SMA. Taken together, our study unravels the cell components and regulatory mechanism of mulberry-like cell clusters in MPE associated with tumor malignant competence.