BHLHE40 and cancer: To further demonstrate that BHLHE40 plays a crucial role in the tumor microenvironment of pancreatic cancer, we identified that BHLHE40 was dramatically hyper-regulated in the majority of immune cells, including mast cells, tumor-associated neutrophile (TAN), pDC, endothelial cell, dendritic cells (DC), ductal cell, cancer associated fibroblasts (CAF), macrophages, natural killer (NK) cells and gamma-delta T cells by single-cell RNA sequencing analysis (Fig. 8A–C).