title: Influence of interferon-alpha combined with chemo (radio) therapy on immunological parameters in pancreatic adenocarcinoma.
abstract: Prognosis of patients with carcinoma of the exocrine pancreas is particularly poor. A combination of chemotherapy with immunotherapy could be an option for treatment of pancreatic cancer. The aim of this study was to perform an immunomonitoring of 17 patients with pancreatic cancer from the CapRI-2 study, and tumor-bearing mice treated with combination of chemo (radio) therapies with interferon-2α. Low doses of interferon-2α led to a decrease in total leukocyte and an increase in monocyte counts. Furthermore, we observed a positive effect of interferon-2α therapy on the dendritic cells and NK (natural killer) cell activation immediately after the first injection. In addition, we recorded an increased amount of interferon-γ and IL-10 in the serum following the interferon-2α therapy. These data clearly demonstrate that pancreatic carcinoma patients also show an immunomodulatory response to interferon-2α therapy. Analysis of immunosuppressive cells in the Panc02 orthotopic mouse model of pancreatic cancer revealed an accumulation of the myeloid-derived suppressor cells in spleens and tumors of the mice treated with interferon-2α and 5-fluorouracil. The direct effect of the drugs on myeloid-derived suppressor cells was also registered in vitro. These data expose the importance of immunosuppressive mechanisms induced by combined chemo-immunotherapy.
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Svetlana.karakhanova@med.uni-heidelberg.de.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Karakhanova
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. beate.mosl@med.uni-heidelberg.de.
authors.forename: Beate
authors.initials: B
authors.lastname: Mosl
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Dirk.Jaeger@med.uni-heidelberg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Harig
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. katharinavonahn@hotmail.com.
authors.forename: Katharina
authors.initials: K
authors.lastname: von Ahn
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. jasminfritz@web.de.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Fritz
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Jan.Schmidt@hirslanden.ch.
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: National Centre for Tumor Disease, University Hospital Heidelberg, 69120 Heidelberg, Germany. Dirk.Jaeger@med.uni-heidelberg.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.affiliation: Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, 81377 Munich, Germany. jens.werner@med.uni-heidelberg.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. Alexandr.bazhin@med.uni-heidelberg.de.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Bazhin
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D020014:K562 Cells; D007958:Leukocyte Count; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D002945:Cisplatin; D005472:Fluorouracil