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. 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 chemo-therapeutic 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.