The impact of whole glucan particles (WGP) treatment on pancreatic myeloid cells

Despite the remarkable success of immunotherapy in many types of cancer, pancreatic cancer has yet to benefit. Innate immune cells are critical players in antitumor immunosurveillance. Recent studies have revealed that innate immune populations may possess a form of memory, termed trained immunity through transcriptomic, epigenetic, and metabolic reprograming. 1Here, we show that intraperitoneal administration of yeast-derived particulate β-glucan results in 90% of that dose trafficking to the pancreas. This trafficking leads to a robust influx of newly characterized innate immune cells with an inflammatory monocyte/macrophage phenotype into the pancreas in a CCR2 dependent manner. These cells also exhibit a trained immunity phenotype upon exposure to tumor-derived factors and show enhanced phagocytosis and ROS-mediated cytotoxicity against pancreatic tumors. In orthotopic models of pancreatic cancer, mice trained with β-glucan show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with anti-PD-L1 immunotherapy. Cumulatively, these findings highlight a novel trafficking mechanism of yeast-derived particulate β-glucan that incites a phenotype of trained immunity specifically in the pancreas that can be utilized as an innovative strategy to treat pancreatic cancer. mouse pancreatic myeloid cells in triplicate treated with whole glucan particles (WGP) and untreated mouse pancreatic myeloid cells in triplicate