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Role of Immune Cells and Immune-Based Therapies in Pancreatitis and Pancreatic Ductal Adenocarcinoma

Journal

GASTROENTEROLOGY
Volume 144, Issue 6, Pages 1230-1240

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2012.12.042

Keywords

Acute Pancreatitis; Chronic Pancreatitis; Pancreatic Ductal Adenocarcinoma

Funding

  1. National Institutes of Health Grant [R01 DK092421, K23 CA148964-01]
  2. Digestive Disease Center [DK56339]
  3. Robert Wood Johnson Foundation
  4. Johns Hopkins School of Medicine Clinical Scientist Award
  5. National Pancreas Foundation
  6. Lefkofsky Family Foundation
  7. NCI SPORE in Gastrointestinal Cancers [P50 CA062924-14]
  8. Lustgarten Foundation
  9. Viragh Foundation
  10. Skip Viragh Pancreatic Cancer Center at Johns Hopkins
  11. Sol Goldman Pancreatic Cancer Center
  12. Dana and Albert Cubby Broccoli Endowed Professorship

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Immune cells are important in the pathogenesis of acute pancreatitis and determine disease severity. Results from cytokine-based clinical trials for acute pancreatitis have been disappointing, so strategies that target and alter the behavior of infiltrating immune cells require consideration. Recurrent acute pancreatitis can progress to chronic pancreatitis, which is a well-described risk factor for pancreatic ductal adenocarcinoma (PDA). However, most patients with chronic pancreatitis do not develop PDA, and most patients with PDA do not have a history of pancreatitis. Interestingly, chronic pancreatitis and PDA tissues have similarities in their desmoplasia and inflammatory infiltrates, indicating overlapping inflammatory responses. Further studies are needed to determine the differences and similarities of these responses, improve our understanding of PDA pathogenesis, and develop specific immune-based therapies. Immune cells in PDA produce immunosuppressive signals that allow tumors to evade the immune response. Unlike single therapeutic agent studies that block immunosuppressive mechanisms, studies of combination therapies that include therapeutic vaccines have provided promising results.

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