title: Interferon-alpha restitutes the chemosensitivity in pancreatic cancer.
abstract: BACKGROUND
  Multidrug resistance is a major obstacle in the treatment of pancreatic cancer. Immunochemotherapy including interferon-alpha increases response rates and survival.
  
  
  METHODS
  Pancreatic cancer was induced in an orthotopic mouse model. Animals received standard chemotherapy or combinative treatment with interferon-alpha. Expression and function of drug-resistance proteins were analyzed. Immunological phenotyping, cytotoxic activity assays and analysis of T-cell activation status were performed.
  
  
  RESULTS
  Addition of interferon-alpha to chemotherapeutic regimes significantly reduced chemotherapy-induced expression of multidrug resistance proteins and drug efflux activity of cancer cells. Tumor size and metastatic seeding decreased significantly upon combination therapy and survival was prolonged. A significantly higher proportion of activated and cytotoxic active CD8+ tumor infiltrating lymphocytes was detectable after induction of drug resistance.
  
  
  CONCLUSIONS
  Restitution of chemosensitivity by the addition of interferon alpha to chemotherapy was demonstrated in experimental pancreatic cancer for the first time. Since drug-resistance proteins may function as tumor antigens, our data support immunochemotherapy as an encouraging new approach.
authors.affiliation: Department of General Surgery, Ruprecht Karls University of Heidelberg, 69120 Heidelberg, Germany. katrin.hoffmann@med.uniheidelberg.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Hoffmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Mehrle
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Angela
authors.initials: A
authors.lastname: Märten
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000093542:Gemcitabine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016898:Interferon-alpha; D003841:Deoxycytidine; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine