Impact of interferon-alpha in combined chemoradioimmunotherapy for pancreatic adenocarcinoma (CapRI): First data from the immunomonitoring

Data from a phase II trial combining chemoradiotherapy with IFN-alpha (CapRI scheme) for adjuvant treatment of pancreatic carcinoma are very encouraging. Therefore, a phase III trial comparing chemotherapy with the CapRI scheme has been initiated in August 2004. Translational research with a focus on immunomodulation is performed in parallel to the study.

Blood and serum samples are taken at various time-points. Patients in arm A (chemoradioimmunotherapy) receive a single low-dose-Interferon (LDI) injection prior to therapy to investigate the direct effect of IFN-alpha. Samples from so far 44 patients have been investigated for surface molecule expression, cytokine levels, Natural Killer cell cytotoxicity and antigen-specific Granzyme B release.

Patients in arm A showed one day after IFN-alpha injection a significant increase in spontaneous cytotoxicity; this effect was fading after repeated injections. Furthermore, cells releasing Granzyme B after stimulation with CA 19.9 and MUC-1 protein increased under therapy. Five days after the first IFN-alpha injection IL-12 and TNF-alpha serum levels peak. Furthermore, we observed significant increases of monocytes, peripheral dendritic cells (pDC), CD40+ cells, central and effector memory T cells and CD8 cells, CD4 cells decreased during therapy. All these effects were only observed in arm A patients none of them in arm B patients.

In conclusion, in a translational research project accompanying a challenging multimodality treatment trial including IFN-alpha, we observed an immediate activation of antigen-presenting cells and NK cells followed later on by antigen-specific activation. It will be most interesting if the immune data will show a correlation with the clinical course.