Inducing Antitumor T Cell Immunity: Comparative Functional Analysis of Interstitial Versus Langerhans Dendritic Cells in a Human Cell Line Model

Abstract

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.

Arming the Melanoma Sentinel Lymph Node through Local Administration of CpG-B and GM-CSF: Recruitment and Activation of BDCA3/CD141+ Dendritic Cells and Enhanced Cross-Presentation

“…Both subsets were previously reported to be able to migrate to draining LNs and to prime specific Th cells or CTLs (21,22). Besides these two migratory subsets, we also identified two CD1a À LN-resident cDC subsets (CD14 À or CD14 þ ; ref.…”

A role for multidrug resistance protein 4 (MRP4; ABCC4) in human dendritic cell migration

“…However, MRP4 protein expression was detected on MUTZ3 progenitor cells and on in vitro cultured immature and mature MUTZ3-DCs and MUTZ3-LCs by immunocytochemistry (data not shown). Because the MUTZ3 cell line functions as a previously described relevant model for in vitro 19,29,30 this cell line was used for further in vitro MRP4 studies. Given the notion that a previous study by Angénieux et al 31 reported MRP4 mRNA expression in MoDC, mRNA levels were also checked by semiquantitative RT-PCR for monocytes and MUTZ3 progenitors as well as for differentiated MoDC and MUTZ3-DCs and MUTZ3-LCs.…”

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases

“…Moreover, cytokine receptors that are associated with DC differentiation such as GM-CSF-R and TNF-α-RI and -RII are up-regulated. In contrast to other AML-derived cell lines, MUTZ-3 cells have a marked DC differentiation capacity since CD1a expression after DC differentiation ranges between 60% and 90% for MUTZ-3 IDC and LC, respectively (66,67). Moreover, MUTZ-3-generated IDC and LC also express intermediate to high levels of co-stimulatory, adhesion, and MHC class I and II molecules, indicating that MUTZ-3 IDC and LC exhibit a true DC phenotype (68).…”