Dendritic cells as potential adjuvant for immunotherapy in adrenocortical carcinoma

Authors


Matthias Schott, Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Moorenstr.5, D-40225 Duesseldorf, Germany, Tel.: 49 2118117810; Fax: 49 2118117860; E-mail: schottmt@uni-duesseldorf.de

Summary

Objective  Adrenocortical carcinoma (ACC) is a rare malignancy associated with a dismal prognosis. Dendritic cells (DCs) are professional antigen-presenting cells leading to an antitumour immune response. The aim of this study was to elaborate two methods of antigen delivery to DCs and to evaluate an immunotherapy protocol in ACC patients.

Design/patients  Autologous DCs were pulsed with autologous tumour lysate (TL). Fusion of DCs with tumour cells was based on a polyethylene glycol method. Two patients with metastasized hypersecretory ACC were vaccinated twice.

Measurements In vitro data were quantified by measurement of PBMC (peripheral blood mononuclear cell) responses and cytokine secretion and by flow cytometry analyses. Clinical response was monitored by CT scan of tumour mass and measurement of angiogenic factors.

Results  The maximum loading of TL was obtained at 24 h as 48·2% (± 26·8%) of DCs were TL-positive. The DC/tumour cell fusion efficacy was ∼45% as shown by double positive staining for ACTH receptor and DC-specific CD83. In vivo DC vaccination resulted in positive delayed-type hypersensitivity skin reactions reflecting specific memory T-lymphocyte reaction. In vitro analyses revealed specific T-cell proliferation in patient 1 (stimulation index: 5·7 compared to pretreatment) and induction of cytotoxic granzyme B secreting T cells in patient 2 (0·41% CD8 + cells vs. 0·06% pretreatment) as indicators of specific cytotoxic T cells. Although angiogenic serum markers could be stabilized, no impact on tumour growth could be observed.

Conclusion  Our data demonstrate that autologous dendritic cells induce antigen-specific Th1 immunity in adrenocortical carcinoma. The clinical outcome, however, was not improved in the patients studied here.

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