Dendritic cells as potential adjuvant for immunotherapy in adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare malignancy associated with dismal prognosis. The low response rates of different therapy approaches emphasize the need to search for novel treatment modalities. Dendritic cells (DCs) are professional antigen-presenting cells, which have been successfully used to induce anti-tumor immunity in humans. Antigen delivery to DCs was achieved with specific tumor antigens as well as with autologeous tumor lysate (TL) and by fusion of autologeous tumor cells with DCs. Here, we report on the evaluation of two methods to improve antigen delivery for an in-vivo immunotherapy in ACC. The up-take of FITC-labeled autologeous tumor lysate (TL) were measured in DCs pulsed up to 48h. The maximum loading was obtained at 24h as 42–85% of DCs were TL-positive with a mean fluorescence intensity of 65–100 (compared to 3 in controls). In parallel, a fusion protocol with polyethylene glycol was established by using an ACC cell line (NCI-H295R) and a DC-like cell line (TF-1). The fusion efficacy was ~45% as shown for positive staining of ACTH receptor as well as for DC-specific CD83. Moreover, two patients with metastasised hypersecretory ACC were treated with TL-pulsed DCs. Positive delayed-type hypersensitivity skin reaction in both patients suggested the presence of antigen-specific memory T-lymphocytes. Moreover, in vitro analyses revealed a specific T-cell proliferation (5.7-fold increase compared to pretreatment) in patient 1 and the induction of cytotoxic granzyme B secreting T-cells (0.41% CD8 positive cells vs. 0.06% before therapy) in patient 2 as indicators of specific cytotoxic T-cells. No adverse effects were observed in both patients. Although autologeous DCs induced a specific Th1 immunity in metastasized ACC patients and angiogenic serum markers (PDGF-BB and VEGF) decreased or did not significanctly change, no impact on tumor growth could be observed. Irrespective of the clinical outcome our data clearly demonstrate that autologeous DCs may induce a specific Th1 immunity in ACC where no effective therapy is available thus far.