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

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 crosspresentation 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-a (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 melanomaspecific 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.

Transcutaneous and intradermal vaccination

“…In vitro, DDCs and LCs derived from CD34 pos cells loaded with tumor antigens can also stimulate in a single cycle memory CD8 pos T cells of patients with metastatic melanoma to transform them into CTLs. 65 J. Banchereau's group confirmed these results for the interstitial LCs and DCs derived from human skin explants. Nonetheless, these DDCs are less able than LCs to cross-present influenza virus matrix protein in vitro.…”

“…Ex vivo studies conducted on CD14 pos DCs and CD1a pos LCs generated in vitro from human hematopoietic precursors(CD34 pos ) have showed that these two cell types were capable of capturing, in an identical manner, antigens from necrotic or apoptotic tumor cells (melanoma). 65 However, these capture mechanisms can differ according to the type of APC. LCs are now recognized as effective actors in endocytosis.…”

Primary Human Immunodeficiency Virus Type 1-Specific CD8+T-Cell Responses Induced by Myeloid Dendritic Cells

“…ϩ T cells to melanoma antigen (6). Furthermore, there is a subpopulation of CD1a ϩ CD14 Ϫ CD207 Ϫ dermal DC that activate antigen-specific CD8 ϩ T cells less efficiently than LC (32).…”

Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer

“…CD34-DCs that are less homogenous than MoDCs, contain two major myeloid DC subsets, i.e. Langerhans cells and interstitial dermal-type DC, and seem able to achieve a large immune response (36,37). Interestingly, DC-based immunotherapy can be also combined to IL-2 administration (24,38) or to anti-angiogenic drugs that have recently proven their efficiency in the treatment of advanced RCCs (39).…”