Abstract
Human Plasmacytoid Dendritic Cells (PDCs) infiltrating solid tumor tissues and draining lymph nodes of Head and Neck Squamous Cell Carcinoma (HNSCC) show an impaired immune response. In addition to an attenuated secretion of IFN-α little is known about other HNSCC-induced functional alterations in PDCs. Particular objectives in this project were to gain new insights regarding tumor-induced phenotypical and functional alterations in the PDC population. We showed by FACS analysis and RT-PCR that HNSCC orchestrates an as yet unknown subpopulation exhibiting functional autonomy in-vitro and in-vivo besides bearing phenotypical resemblance to PDCs and T cells. A subset, positive for the PDC markers CD123, BDCA-2, HLA-DR and the T cell receptor αβ (TCR-αβ) was significantly induced subsequent to stimulation with HNSCC in-vitro (p = 0.009) and also present in metastatic lymph nodes in-vivo. This subgroup could be functionally distinguished due to an enhanced production of IL-2 (p = 0.02), IL-6 (p = 0.0007) and TGF-β (not significant). Furthermore, after exposure to HNSCC cells, mRNA levels revealed a D-J-beta rearrangement of the TCR-beta chain besides a strong enhancement of the CD3ε chain in the PDC population. Our data indicate an interface between the PDC and T cell lineage. These findings will improve our understanding of phenotypical and functional intricacies concerning the very heterogeneous PDC population in-vivo.
Highlights
Dendritic cells (DCs) are bone marrow derived antigen presenting cells, such as B cells and monocytes and appear to be indispensable for initiating appropriate immune responses
Phenotypical alterations in the plasmacytoid dendritic cells (PDCs) population subsequent to incubation with Head and Neck Squamous Cell Carcinoma (HNSCC) cell-lines in-vitro were narrowed to incomplete maturation and upregulation of the receptors CD4 and CD45RA
Classical PDC maturation is phenotypically defined by the upregulation of CD123, CD80, CD83, CD86 and HLA-DR in addition to the down-regulation of the C-type Lectin BDCA-2 [14,15,16]
Summary
Dendritic cells (DCs) are bone marrow derived antigen presenting cells, such as B cells and monocytes and appear to be indispensable for initiating appropriate immune responses. A complicated trafficking system leads them from the bone marrow through the bloodstream to distinct peripheral tissues, where different immature DC populations reveal unique kinds of chemokine responsiveness [1] They migrate to lymphoid organs in order to present processed antigens to lymphocytes and to stimulate immune responses [2]. Two main human DC subsets are to be distinguished: myeloid dendritic cells (MDCs) including Langerhans cells, dermal dendritic cells and interstitial DCs versus plasmacytoid dendritic cells (PDCs) [3] Referring to their plasma cell-like appearance PDCs were first identified as ‘Plasmacytoid monocytes/T cells’ in T cell areas of lymphoid organs, later in peripheral blood and tonsils [4]. Different PDC subsets with distinct phenotype und functions have been identified [8,9]
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