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Updated: Jul 3, 2026
Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Interferon-alpha restitutes the chemosensitivity in pancreatic cancer
Katrin Hoffmann1, Stefan Mehrle, Jan Schmidt
1Department of General Surgery, Ruprecht Karls University of Heidelberg, 69120 Heidelberg, Germany. katrin.hoffmann@med.uniheidelberg.de
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.
