Efferocytosis: A Driver of Liver Metastasis in Pancreatic Cancer

This study reveals how efferocytosis, the process by which macrophages clear apoptotic cells, supports pancreatic ductal adenocarcinoma (PDAC) liver metastasis. Researchers found that low-grade tissue injury during hepatic colonization triggers macrophage reprogramming through efferocytosis. Progranulin, a key factor expressed by macrophages, regulates this process by controlling lysosomal acidification and degradation of apoptotic cargo, leading to LXRα/RXRα-mediated macrophage conversion and upregulation of arginase 1, which suppresses anti-tumor immunity. Disrupting efferocytosis pharmacologically or genetically depleting progranulin in macrophages improved CD8+ T-cell function and reduced liver metastases. These findings highlight the dual role of macrophages in tissue repair and cancer progression, identifying efferocytosis and progranulin as promising therapeutic targets to combat PDAC metastasis.