Expression of the T cell receptor αβ on a CD123+ BDCA2+ HLA-DR+ subpopulation in head and neck squamous cell carcinoma

• Published in: PloS one Vol. 6; no. 1; p. e15997
• Main Authors: Thiel, Annette, Kesselring, Rebecca, Pries, Ralph, Puzik, Alexander, Wittkopf, Nadine, Wollenberg, Barbara
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.01.2011; Public Library of Science (PLoS)
• Subjects: Antigens; Antigens, Surface; Autonomy; Biology; Bone marrow; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; CD123 antigen; Cell Lineage; Chains; Dendritic cells; Epidermal growth factor; Extracellular matrix; Flow cytometry; Genotype & phenotype; Head; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; Histocompatibility antigen HLA; HLA-DR Antigens - immunology; Humans; Immune response; Immune system; Interferon; Interleukin 2; Interleukin 6; Interleukin-3 Receptor alpha Subunit - immunology; Lectins, C-Type - immunology; Lymph nodes; Lymphocytes; Lymphocytes T; Medicine; Membrane Glycoproteins - immunology; Metastases; mRNA; Otolaryngology; Polymerase chain reaction; Population; Receptors, Antigen, T-Cell, alpha-beta - analysis; Receptors, Immunologic - immunology; Solid tumors; Squamous cell carcinoma; T cell receptors; T-cell receptor; Tissues; Transcription factors; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0015997

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.