Myeloid Dendritic Cells from Human Cutaneous Squamous Cell Carcinoma Are Poor Stimulators of T-Cell Proliferation

To determine the phenotype and function of myeloid dendritic cells (DCs) from human cutaneous squamous-cell carcinoma (SCC), we studied their surface marker expression and allo-stimulatory potential ex vivo. There were abundant CD11c+ myeloid DCs, as well as TNF and inducible nitric oxide synthase (...

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Bibliographic Details
Published in:Journal of investigative dermatology 2009-10, Vol.129 (10), p.2451-2462
Main Authors: Bluth, Mark J., Zaba, Lisa C., Moussai, Dariush, Suárez-Fariñas, Mayte, Kaporis, Helen, Fan, Linda, Pierson, Katherine C., White, Traci R., Pitts-Kiefer, Alexander, Fuentes-Duculan, Judilyn, Guttman-Yassky, Emma, Krueger, James G., Lowes, Michelle A., Carucci, John A.
Format: Article
Language:English
Subjects:
Antigens, CD1 - metabolism
Biological and medical sciences
Cell Proliferation
Cells, Cultured
Dendritic Cells - metabolism
Dendritic Cells - pathology
Dermatology
HLA-DR Antigens - metabolism
Humans
Langerhans Cells - metabolism
Langerhans Cells - pathology
Lectins, C-Type - metabolism
Medical sciences
Membrane Glycoproteins - metabolism
Neoplasms, Squamous Cell - metabolism
Neoplasms, Squamous Cell - pathology
Nitric Oxide Synthase Type II - metabolism
Receptors, Immunologic - metabolism
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
Tumor Necrosis Factor-alpha - metabolism
Tumors of the skin and soft tissue. Premalignant lesions
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Summary:To determine the phenotype and function of myeloid dendritic cells (DCs) from human cutaneous squamous-cell carcinoma (SCC), we studied their surface marker expression and allo-stimulatory potential ex vivo. There were abundant CD11c+ myeloid DCs, as well as TNF and inducible nitric oxide synthase (iNOS)-producing DCs, in and around SCC tumor nests. Although myeloid DCs from SCC, adjacent non-tumor-bearing skin, and normal skin, were phenotypically similar by flow cytometry, and there was a pronounced genomic signature of mature DCs in SCC, they showed different T-cell stimulatory potential in an allogeneic mixed leukocyte reaction. Myeloid DCs from SCC were less potent stimulators of allogeneic T-cell proliferation than DCs from non-tumor-bearing skin. Culture with a DC-maturing cytokine cocktail (IL-1β, IL-6, TNF-α, and PGE2) enhanced stimulatory potential in DCs from non-tumor-bearing skin, whereas SCC-associated DCs remained poor stimulators of T-cell proliferation. The microenvironment associated with SCC showed expression of TGF-β, IL-10, and VEGF-A, factors capable of suppressing the DC function. These findings indicate that CD11c+/HLA-DRhi DCs from SCC are mature, but are not potent stimulators of T-cell proliferation compared with phenotypically similar DCs isolated from non-tumor-bearing skin. Identification of mechanisms responsible for suppression of tumor-associated DCs may provide insight into the evasion of immunosurveillance by SCC.
ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2009.96