胰腺癌
免疫监视
先天免疫系统
胰腺
免疫
免疫系统
免疫疗法
癌症研究
医学
癌症
胰腺肿瘤
腺癌
免疫学
生物
内科学
作者
Anne E. Geller,Rejeena Shrestha,Matthew R. Woeste,Haixun Guo,Xiao Hu,Chuanlin Ding,Kalina Andreeva,Julia H. Chariker,Mingqian Zhou,David Tieri,Corey T. Watson,Robert A. Mitchell,Huang‐Ge Zhang,Yan Li,Robert C.G. Martin,Eric C. Rouchka,Jun Yan
标识
DOI:10.1038/s41467-022-28407-4
摘要
Abstract Despite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate β-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, β-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer.
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