title: Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?
abstract: BACKGROUND
  Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most common pancreatic cancer, is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence.
  
  
  METHODS
  We examined the systemic influence ductal pancreatic adenocarcinoma (PDAC) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors, chronic pancreatitis, and age-matched controls.
  
  
  RESULTS
  All groups examined, including PDAC, had decreased levels of myeloid DCs (MDC) and plasmacytoid DCs (PDC) and enhanced apoptosis in these cells as compared to controls. We found elevated levels of PGE2 and CXCL8 in subjects with PDAC, and chronic pancreatitis. Levels of these inflammatory factors were in part restored in PDAC after tumor resection, whereas the levels of DCs were impaired in the majority of these patients approximately 12 weeks after tumor removal. Our results prove that solid pancreatic tumors, including PDAC, systemically affect blood DCs. The impairments do not seem to be tumor-specific, since similar results were obtained in subjects with chronic pancreatitis. Furthermore, we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival.
  
  
  CONCLUSIONS
  Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs. Furthermore, the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival.
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Vegard
authors.initials: V
authors.lastname: Tjomsland
authors.forename: Per
authors.initials: P
authors.lastname: Sandström
authors.forename: Anna
authors.initials: A
authors.lastname: Spångeus
authors.forename: Davorka
authors.initials: D
authors.lastname: Messmer
authors.forename: Johan
authors.initials: J
authors.lastname: Emilsson
authors.forename: Ursula
authors.initials: U
authors.lastname: Falkmer
authors.forename: Sture
authors.initials: S
authors.lastname: Falkmer
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
authors.forename: Kurt
authors.initials: K
authors.lastname: Borch
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007107:Immune System; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal