Pancreatic cancer is basically a hard-to-treat disease. As the fourth leading cause of cancer deaths, pancreatic cancer is blamed for 7% of all cancer-related deaths. Pancreatic ductal adenocarcinoma (PDA), the predominant form of pancreatic cancer, makes up the vast majority of all pancreatic cancer cases.
Now an article “Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance” published online 10 April 2017 in Nature Medicine reveals a mechanism that PDA uses to escape the body’s immune attack. This will lead to a new strategy for developing immunotherapies for the fatal disease. George Miller at the New York University School of Medicine is the senior author of the article.
Miller and colleagues carried out experiments in mouse models and accessed data of human patients, finding that two proteins, dectin-1 and galectin-9, are present in large amounts in pancreatic tumors. Further, the interactions between them inhibits the function of macrophages, a type of white blood cells that ingest foreign material. Macrophages are key players in immune response to foreign invaders. The researchers found that PDA patients with increased galectin-9 tend to have worse survival.
Using a mouse model of PDA, the researchers compared mice that produced dectin-1 with those that did not, and found that mice without dectin-1 survived for a longer period of time. Treatment with and antibody that inhibits the galectin-9/dectin-1 interaction significantly shrank tumors and prolonged the mice’s survival.
The protein dectin-1 is believed to play a role in innate immune responses to fungal pathogens. This receptor mediates many cellular functions, such as enhancing cytokine production in macrophages and regulating T-cell activation and proliferation. However, the role of dectin-1 in sterile inflammation and oncogenesis remains largely unknown. (Cusabio offers proteins like dectin-1 and galectin 9, as well as antibodies like FITC conjugated antibody.)
This study extends our understanding of dectin-1. The researchers found that dectin-1 is able to ligate the lectin galectin 9 in mouse and human PDA, leading to tolerogenic macrophage programming and adaptive immune suppression. This may explain why pancreatic cancer is so aggressive. The researchers also found that targeting dectin 1 signaling could be a treatment strategy for PDA.
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