gms | German Medical Science

Objective: Vaccination with dendritic cells (DC) has yielded promising results in a variety of human cancers. We have previously shown that functionally competent DC can be generated from CD14+ monocytes in patients with high grade glioma (HGG). When loaded with autologous tumor lysate, these DC induce anti-tumoral immune responses in vitro. Here, the results of clinical application of DC immunotherapy are presented.

Methods: DC vaccines were generated from four patients with HGG and administered following neurosurgical resection. Blood samples were collected before and during immunotherapy. Immunomonitoring consisted of flow cytometric evaluation of major immune cell subsets, including CD107a+ cytotoxic effector cells (CTL) and FoxP3+ regulatory T cells (Treg). Anti-tumoral immunity was detected by IFNγ-ELISPOT.

Results: Vaccination was well tolerated. Analyses of peripheral blood leukocytes were stable throughout vaccination without any signs of hematotoxicity. A significant increase in CD107a+ CTL was detected in two patients. CD4+CD25+ T-cells increased, with FoxP3+ Tregs accounting for about 80% of the population in all patients. PBMC from three patients exhibited increased IFN? responses in correlation with the number of administered DC vaccines.

Conclusions: DC vaccination in patients with HGG does not elicit severe adverse events. In respect to surrogate parameters of vaccine efficiency, a significantly increased CTL activity as well as a tumor-specific effector cell response generated in vivo were detected. However, vaccination also expanded Tregs, which are considered counterproductive to tumor destruction by CTL. These data advocate further immunotherapy trials in HGG to correlate immune response with outcome, while emphasising the importance of monitoring Tregs.