Myeloid dendritic cells from human squamous cell carcinoma are poor stimulators of T cell proliferation

In order to determine the phenotype and function of myeloid 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)-p...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of investigative dermatology 2009-04, Vol.129 (10), p.2451-2462
Hauptverfasser: 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: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:In order to determine the phenotype and function of myeloid 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 (TIP-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 allo-MLR. 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, and PGE 2 ) enhanced stimulatory potential in DCs from non-tumor-bearing skin, while SCC associated DCs remained poor stimulators of T cell proliferation. The microenvironment associated with SCC showed expression of TGFβ, IL-10 and VEGF-A, factors capable of suppressing DC function. These findings indicate that CD11c + /HLA-DR hi 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 evasion of immunosurveillance by SCC.
ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2009.96