title: TRAIL Promotes Tumor Growth in a Syngeneic Murine Orthotopic Pancreatic Cancer Model and Affects the Host Immune Response.
abstract: OBJECTIVE
  Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is currently being evaluated as a possible biological agent for cancer treatment. However, many tumor cells are resistant to TRAIL-induced apoptosis. In these cases, TRAIL may activate different pathways promoting tumor growth as well as showing different interactions with the immunological tumor microenvironment. In this study, the impact of TRAIL on tumor growth and survival in a syngeneic model of TRAIL-resistant pancreatic cancer cells was investigated.
  
  
  METHODS
  Murine 6606PDA pancreatic cancer cells were injected into the pancreatic heads of TRAIL mice and their littermates. To examine a direct effect of TRAIL on tumor cells, cultures of 6606PDA were TRAIL stimulated.
  
  
  RESULTS
  The TRAIL mice displayed significantly decreased tumor volumes and an enhanced overall survival in pancreatic cancer. The decreased tumor growth in TRAIL mice was accompanied by a decrease of regulatory CD4 cells within tumors. Concordantly, TRAIL treatment of wild-type mice enhanced tumor growth and increased the fraction of regulatory CD4 cells. Yet, a direct effect of TRAIL on 6606PDA cells was not detected.
  
  
  CONCLUSIONS
  Thus, TRAIL can promote tumor growth in TRAIL-resistant tumor cells. This may restrict possible future clinical applications of TRAIL in pancreatic cancer.
authors.affiliation: From the *Departments of General, Visceral, Thoracic and Vascular Surgery and †Medicine A (Gastroenterology and Nephrology), University Medicine Greifswald, Ernst-Moritz-Arndt-University, Greifswald, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Beyer
authors.forename: Lars
authors.initials: L
authors.lastname: Normann
authors.forename: Matthias
authors.initials: M
authors.lastname: Sendler
authors.forename: Andre
authors.initials: A
authors.lastname: Käding
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Heidecke
authors.forename: Lars Ivo
authors.initials: LI
authors.lastname: Partecke
authors.forename: Wolfram
authors.initials: W
authors.lastname: von Bernstorff
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D053320:Receptors, Tumor Necrosis Factor, Member 10c / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014185:Transplantation, Isogeneic; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand