BACKGROUND: Multidrug resistance is a major obstacle in the treatment of pancreatic cancer. Immunochemotherapy including interferon-alpha increases response rates and survival. MATERIALS AND 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. CONCLUSION: 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.
BACKGROUND: Multidrug resistance is a major obstacle in the treatment of pancreatic cancer. Immunochemotherapy including interferon-alpha increases response rates and survival. MATERIALS AND 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. CONCLUSION: 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: Christopher J LaRocca; Joohee Han; Tatyana Gavrikova; Leonard Armstrong; Amanda R Oliveira; Ryan Shanley; Selwyn M Vickers; Masato Yamamoto; Julia Davydova Journal: Surgery Date: 2015-02-27 Impact factor: 3.982
Authors: Richard E Royal; Catherine Levy; Keli Turner; Aarti Mathur; Marybeth Hughes; Udai S Kammula; Richard M Sherry; Suzanne L Topalian; James C Yang; Israel Lowy; Steven A Rosenberg Journal: J Immunother Date: 2010-10 Impact factor: 4.456
Authors: Angela Märten; Jan Schmidt; Jennifer Ose; Sabine Harig; Ulrich Abel; Marc W Münter; Dirk Jäger; Helmut Friess; Julia Mayerle; Guido Adler; Thomas Seufferlein; Thomas Gress; Roland Schmid; Markus W Büchler Journal: BMC Cancer Date: 2009-05-26 Impact factor: 4.430