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* Department of Pathology and
Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands
Dendritic cells (DC) are increasingly applied as a cellular adjuvant in immunotherapy of cancer. Two major myeloid DC subsets are recognized: interstitial DC (IDC) that infiltrate connective tissues and Langerhans cells (LC) that line epithelial surfaces. Yet, functional differences between IDC and LC remain to be defined. We recently showed that the CD34+ acute myeloid leukemia cell line MUTZ-3 supports differentiation of both DC-SIGN+ IDC and Langerin-positive Birbeck granule-expressing LC. By comparative functional characterization of MUTZ-3 IDC and MUTZ-3 LC, we aimed to elucidate the relative abilities of these two DC subsets to induce a specific T cell response and reveal the more suitable candidate for use as a clinical vehicle of tumor vaccines. Although mature LC and IDC displayed comparable lymph node-homing potential, mature LC showed higher allogeneic T cell stimulatory capacity. Nevertheless, IDC supported the induction of tumor Ag-specific CD8+ T cells at an overall higher efficiency. This might be related to the observed inability of LC to release T cell stimulatory cytokines such as IL-12p70, IL-23, and IL-15. Although this inability did not result in a detectable deviation in the cytokine expression profile of primed T cells, transduction with IL-12p70 significantly improved priming efficiency of LC, and ensured a functional equivalence with IDC in this regard. In conclusion, except for the inability of LC to release distinct type 1 T cell stimulatory cytokines, in vitro function of LC and IDC suggests comparable abilities of both subsets for the in vivo induction of antitumor T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Address correspondence and reprint requests to Dr. Rik J. Scheper, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E-mail address: rj.scheper{at}vumc.nl
2 Abbreviations used in this paper used: DC, dendritic cell; IDC, interstitial DC; MoDC, monocyte-derived DC; DDC, dermal DC; LC, Langerhans cell; CEA, carcinoembryonic Ag; PSA, prostate-specific Ag; poly(I:C), polyinosinic-polycytidylic acid; NGFR, nerve growth factor receptor; LN, lymph node.
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