Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma

OBJECTIVE Metastatic neuroendocrine carcinomas of the pancreas frequently f ail to respond to conventional therapies, including radiation and chemother apy. We therefore tested a dendritic cell-based immunotherapy in an attempt to eradicate residual tumour masses in a patient suffering from a metastat ic insulin-producing pancreatic carcinoma. DESIGN Autologous dendritic cells (DCs) were generated from peripheral bloo d monocytes in the presence of granulocyte/macrophage colony-stimulating fa ctor, interleukin-4 and tumour necrosis factor alpha. DCs were loaded with tumour-derived lysate (TL), and were delivered by subcutaneous injections i n 4-week intervals. RESULTS Three weeks after first treatment, the patient developed a strong d elayed-type hypersensitivity (DTH) skin reaction with an erythema and indur ation after the challenge with TL-pulsed DCs, which indicates the efficient generation of antigen-specific memory T-cells. Immunohistochemical analysi s of skin biopsy demonstrated a strong perivascular and epidermal infiltrat ion by T-helper (CD4 positive) and cytotoxic T cells (CD8 positive). Stimul ation with TL revealed a dose-dependent T-cell proliferation with a stimula tion index of 1.1-5.7 compared to 1.1-1.4 before vaccination (P < 0.01). Mo st 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 d etection limit of 0.15 umol/l within 9 months of therapy. The ultrasound ex amination revealed a tumour regression of the metastasis in the right lobe of the liver. CONCLUSIONS Our data indicate that vaccination with tumour lysate-pulsed DC s induced a significant antitumour immune response in a neuroendocrine carc inoma of the pancreas. This approach represents an alternative strategy for the treatment of advanced neuroendocrine carcinomas that are resistant to conventional therapy.