In-depth analysis of pathological function of tumor-associated macrophage populations in hepatic metastatic and primary PDAC

Tumor microenvironment (TME) plays a crucial role in the oncogenesis, early distant metastasis, and limited immunotherapeutic responses of pancreatic ductal adenocarcinoma (PDAC). Myeloid cell populations, particularly tumor-associated macrophages (TAMs), located within this immunosuppressive niche, are pivotal in these processes. With aid of single cell RNA sequencing (scRNA-seq), multiple studies have successfully validated distinct macrophage subtypes pathological functions in different cancer types, yet the correlation of TAMs in hepatic metastatic and primary PDAC lesions remains insufficiently understood. In this study, we reanalyzed samples from both primary and hepatic metastatic PDACs to elucidate the functional conservation and variability of TAMs. Pseudotime trajectory inference, together with pseudobulk analysis based on subtype level, manifests TAMs undergo similar metabolism reprogramming and pro-inflammatory style transitions with specific signaling pathway activations. Compared to primary tumors, hypoxic conditions are alleviated, which largely depends on the physiological context and the preliminary ligand-receptor interactive network within the metastatic niche.