AIM:To determine whether IFN- is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN- for its synergistic properties. METHODS:Eight pancreatic carcinoma cell lines were treated with the single agents and combinations of these. The role of IFN- regarding a) direct inhibitory effects; b) radio and chemosensitizing effects; c) anti-angiogenic properties and d) enhancement of immunogenicity was investigated. RESULTS:Our results show that IFN- has direct inhibitory properties and some synergistic influence as determined by AnnexinV/PI stain and cell count. IFN- is also able to prevent the increase in proliferation rate and VEGF secretion of CDDP resistant cells. Having taken the results from immunogenicity experiments together, we found cells that can be influenced by IFN- but were less susceptible against T cells. Furthermore, high expression of MHC molecules, CD118, EGF-R and Fas was predictive for a good response. CONCLUSION:In conclusion, IFN- has direct cytotoxic effects, acts as a radiosensitizer and circumvents tumor cell-regrowth after CDDP treatment. These mechanisms may be responsible for the good clinical outcome of CapRI.

IFN-alpha activates NK cells against pancreatic carcinoma cells and 5-FU treatment makes tumour cells more susceptible. Furthermore, IFN-alpha induces the immunoproteasome with impact on the immunogenicity of pancreatic carcinoma cells. These mechanisms may be responsible for the improved clinical outcome of CapRI.

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