Abstract Acute pancreatitis (AP) is the most common gastrointestinal disorder leading to hospital admission in the United States. Patients who present with recurrent acute pancreatitis are at a very high risk of developing chronic pancreatitis (CP). Patients with CP experience intractable, difficult to treat abdominal pain and the disease is associated with pancreatic acinar cell loss and fibrosis, and can result in exocrine and endocrine insufficiency. CP is also a risk factor for developing pancreatic ductal adenocarcinoma (PDAC). In AP, initial injury signals likely start at the acinar cell level, where injured acinii produce proinflammatory cytokines and chemokines leading to the recruitment of inflammatory leukocytes into the pancreas. One of the initially recruited leukocytes includes neutrophils, which play pathogenic role locally within the pancreas and in distant organs such as the lung. Soon after, inflammatory monocytes follow into the pancreas and differentiate into macrophages with pro-inflammatory properties and exacerbate the pancreatic injury. Earlier and recent studies show that T cells and macrophages are the predominant immune cell infiltrates in CP. Macrophages in CP are found in close proximity to key pro-fibrogenic pancreatic stellate cells. Experimental studies suggest an interaction between the stellate cells and macrophages to promote fibrosis in CP. In contrast to AP, macrophages in CP display alternate activation consistent with immunosuppressive environment associated with CP. Immune cells also play a critical and differential role of anti- and pro-tumor functions in PDAC. For example, immune signals such as IL-22/IL-22R axis are involved in AP, CP, and PDAC but play differential role between the diseases. To get insight into the inflammatory processes involved, we use multiplex based assays to profile immune cells isolated from the pancreas as well as in situ to determine functional and geographic localization. Citation Format: Aida Habtezion. Immune cell signaling in human and mouse pancreas cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I10.