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 chemoradiotherapy with IFN-alpha 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 injection before therapy to investigate the direct effect of IFN-alpha. So far samples from 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 1 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. We observed significant increases of monocytes, peripheral dendritic cells, 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 and 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 natural killer cells followed later on by antigen-specific activation. It will be most interesting if the immunologic data will show a correlation with the clinical course of the patients.
Schmidt
Jan
J
Department of Surgery, University of Heidelberg, Germany.
Jäger
Dirk
D
Hoffmann
Kartin
K
Büchler
Markus W
MW
Märten
Angela
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000532:radiotherapy; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005472:Fluorouracil / Q000008:administration & dosage; D005492:Folic Acid / Q000008:administration & dosage; D053804:Granzymes / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D011446:Prospective Studies
D016207:Cytokines; D016898:Interferon-alpha; D005492:Folic Acid; D053804:Granzymes; D002945:Cisplatin; D005472:Fluorouracil