In this study, we investigated the origin and evolution of tumor-associated macrophages (TAMs) in pancreatic ductal adenocarcinoma (PDAC). TAMs are a diverse group of cells, and their phenotypes and functions are influenced by various factors, which are not yet fully understood. Using inducible monocyte fate-mapping mice, single-cell transcriptomics, and high-dimensional flow cytometry, we traced the transition of monocytes into TAMs during tumor development. We found that monocytes first differentiate into a transient intermediate population of TAMs, which then give rise to two distinct, longer-lived TAM lineages with unique gene expression profiles, phenotypes, and tumor locations. Both transcriptome data and patient tumor samples from PDAC revealed similar TAM populations in humans, with distinct prognostic implications. These findings offer valuable insights into the monocyte-to-TAM transition, which could inform the development of new therapeutic strategies targeting TAMs in PDAC.
DOI: 10.1126/sciimmunol.adk3981
