Both Langerhans cells and interstitial DC cross‐present melanoma antigens and efficiently activate antigen‐specific CTL

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Abstract
Dendritic cells (DC) have a unique capacity to present external antigens to CD8+ T cells, i.e. cross‐presentation. However, it is not fully established whether the ability to cross‐presentation is restricted to a unique subset of DC in humans. Here, we show that two major myeloid DC subsets, i.e. Langerhans cells (LC) and interstitial DC (Int‐DC), have the ability to cross‐present antigens to CD8+ T cells in vitro. LC and Int‐DC were obtained from DC generated by culturing human CD34+‐hematopoietic progenitor cells with GM‐CSF, FLT3‐L, and TNF‐α (CD34‐DC). Both DC subsets were able to capture necrotic/apoptotic allogeneic melanoma cells and present antigens to CD8+ T cells, resulting in efficient priming of naive CD8+ T cells into CTL capable of killing melanoma cells. Strikingly, a single stimulation with either subset (LC or Int‐DC) or total CD34‐DC loaded with necrotic/apoptotic melanoma cells was sufficient to activate melanoma‐specific memory CD8+ T cells obtained from patients with metastatic melanoma to become effective CTL. Thus, this study provides the rationale to use CD34‐DC loaded with necrotic/apoptotic allogeneic melanoma cells in a clinical trial.

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