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 journalArticle

46 Scopus citations

Abstract

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
Volume129
Issue number10
DOIs
StatePublished - Oct 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation'. Together they form a unique fingerprint.

  • Cite this

    Bluth, M. J., Zaba, L. C., Moussai, D., Suárez-Farĩas, M., Kaporis, H., Fan, L., Pierson, K. C., White, T. R., Pitts-Kiefer, A., Fuentes-Duculan, J., Guttman-Yassky, E., Krueger, J. G., Lowes, M. A., & Carucci, J. A. (2009). Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation. Journal of Investigative Dermatology, 129(10), 2451-2462. https://doi.org/10.1038/jid.2009.96