Unraveling pancreatic ductal adenocarcinoma at single-cell resolution with spatial insights: From mechanisms to clinical translation.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, characterized by pronounced cellular heterogeneity, a dense desmoplastic stroma, and a highly immunosuppressive tumor microenvironment (TME). Recent advances in single-cell RNA sequencing (scRNA-seq) have reshaped our understanding of PDAC by characterizing its cellular composition at single-cell resolution. These studies have uncovered complex TME networks involving T cells, myeloid populations, fibroblasts, and malignant epithelial cells, and have provided mechanistic insights into immune evasion, metastatic progression, and therapeutic resistance. Collectively, these findings depict PDAC as a dynamic and interactive ecosystem driven by cellular interactions. In this review, we systematically summarize recent scRNA-seq-based studies addressing PDAC heterogeneity, tumorigenesis, immune remodeling, therapeutic resistance and biomarker discovery. We further discuss integrative single-cell and spatial multi-omics approaches to map the TME of PDAC, providing a framework for understanding PDAC biology at single-cell and spatial resolution.