Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma.
OBJECTIVE
Metastatic neuroendocrine carcinomas of the pancreas frequently fail to respond to conventional therapies, including radiation and chemotherapy. We therefore tested a dendritic cell-based immunotherapy in an attempt to eradicate residual tumour masses in a patient suffering from a metastatic insulin-producing pancreatic carcinoma.


METHODS
Autologous dendritic cells (DCs) were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumour necrosis factor alpha. DCs were loaded with tumour-derived lysate (TL), and were delivered by subcutaneous injections in 4-week intervals.


RESULTS
Three weeks after first treatment, the patient developed a strong delayed-type hypersensitivity (DTH) skin reaction with an erythema and induration after the challenge with TL-pulsed DCs, which indicates the efficient generation of antigen-specific memory T-cells. Immunohistochemical analysis of skin biopsy demonstrated a strong perivascular and epidermal infiltration by T-helper (CD4 positive) and cytotoxic T cells (CD8 positive). Stimulation with TL revealed a dose-dependent T-cell proliferation with a stimulation index of 1.1-5.7 compared to 1.1-1.4 before vaccination (P < 0.01). Most strikingly, DC-based vaccination was accompanied by a steady decrease of the tumour marker chromogranin A from 2.93 umol/l initially to below the detection limit of 0.15 umol/l within 9 months of therapy. The ultrasound examination revealed a tumour regression of the metastasis in the right lobe of the liver.


CONCLUSIONS
Our data indicate that vaccination with tumour lysate-pulsed DCs induced a significant antitumour immune response in a neuroendocrine carcinoma of the pancreas. This approach represents an alternative strategy for the treatment of advanced neuroendocrine carcinomas that are resistant to conventional therapy.
Schott
M
M
Department of Endocrinology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany. schottmt@uni-duesseldorf.de
Feldkamp
J
J
Lettmann
M
M
Simon
D
D
Scherbaum
W A
WA
Seissler
J
J
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D002455:Cell Division; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008297:Male; D018358:Neuroendocrine Tumors / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D020551:Pulse Therapy, Drug; D013601:T-Lymphocytes / Q000187:drug effects; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins