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 Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-07-2274.

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Submitted July 26, 2002
Accepted January 6, 2003

Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen

Michel Gilliet, Martin Kleinhans, Erica Lantelme, Dirk Schadendorf, Guenter Burg, and Frank O Nestle*

Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland
University of Turin, Orbassano, Italy
Dermatooncology Unit, University of Heidelberg, Mannheim, Germany

* Corresponding author; email: nestle{at}derm.unizh.ch.

Dendritic cells (DC) represent the most potent APC of the immune system capable of initiating primary immune responses to neoantigens. Here we characterized the primary CD4 T cell immune response to protein Keyhole Limpet Hemocyanin (KLH) in five metastatic melanoma patients undergoing a tumor peptide-based dendritic cell vaccination trial. Monocyte-derived dendritic cells displaying a semimature phenotype, as defined by surface markers, were loaded ex-vivo with antigen and injected intranodally at weekly intervals for 4 weeks. All patients developed a strong and longlasting DTH-reactivity to KLH, which correlated with the induction of KLH-dependent proliferation of CD4 T cells in-vitro. Secondary in-vitro stimulation with KLH showed significant increase in IFN-{gamma} and IL-2 but not IL-4- , IL-5- nor IL-10-secretion by bulk T cells. On the single cell level, a majority of TH1-cells among in-vitro generated KLH-specific T cell lines confirmed the preferential induction of a KLH-specific type1 T helper immune response. Furthermore, the induction of KLH-specific antibodies of the IgG2 subtype, may reflect the induction of a type 1 cytokine profile in-vivo after vaccination. Our results indicate that intranodal vaccination with semimature DC can prime strong longlasting CD4 T cell responses with a TH1-type cytokine profile in cancer patients.


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