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

Mark J. Bluth, Lisa C. Zaba, Dariush Moussai, Mayte Suárez-Farĩas, Helen Kaporis, Linda Fan, Katherine C. Pierson, Traci R. White, Alexander Pitts-Kiefer, Judilyn Fuentes-Duculan, Emma Guttman-Yassky, James G. Krueger, Michelle A. Lowes, John A. Carucci

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


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 PGE 2) 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-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 the evasion of immunosurveillance by SCC.

Original languageEnglish (US)
Pages (from-to)2451-2462
Number of pages12
JournalJournal of Investigative Dermatology
Issue number10
StatePublished - Oct 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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