Pancreatic Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Pancreatic Cancer, including details on symptoms, causes, treatment, information.

Immunomodulatory impact of interferon-alpha in combination with chemoradiation of pancreatic adenocarcinoma (CapRI).

Schmidt J, Patrut EM, Ma J, Jäger D, Knaebel HP, Büchler MW, Märten A

Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany.

BACKGROUND: Data from a phase II trial combining chemoradiotherapy with interferon-alpha (IFN-alpha) (CapRI scheme) for adjuvant treatment of pancreatic carcinoma are very encouraging. METHODS: Eight human ductal pancreatic carcinoma cell lines were treated with the CapRI scheme [5-fluorouracil (5-FU), Cisplatin, IFN-alpha and radiation]. Natural killer (NK) and T cells preincubated with IFN-alpha were tested in cytotoxicity assays against these cell lines and the mechanism of cell lysis was investigated. The induction of the immunoproteasome in tumour cells after IFN-alpha stimulation was analysed by immunoblot and RT-PCR. RESULTS: IFN-alpha activated NK cells and increased their cytotoxicity. This cytotoxicity was mediated as well by Fas-induced apoptosis as by perforin release. Pre-treatment of tumour cells with 5-FU and combinations showed a significant increase in the susceptibility of tumour cells against NK cells. Treatment of tumour cells with IFN-alpha induced a switch to the immunoproteasome and enhanced their vulnerability to T cells. This is the first description of this phenomenon in pancreatic carcinoma cells with implications for their immunogenicity. DISCUSSION: 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.

Published 9 August 2006 in Cancer Immunol Immunother, 55(11): 1396-405.
Full-text of this article is available online (may require subscription).

© 2004-2008 Pancreatic Cancer Research Today. All Rights Reserved.