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

Overview

MeSH Major

  • Cell Proliferation
  • Dendritic Cells
  • Neoplasms, Squamous Cell
  • Skin Neoplasms
  • T-Lymphocytes

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-1beta, IL-6, TNF-alpha, 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-beta, 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.

publication date

  • October 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2846605

Digital Object Identifier (DOI)

  • 10.1038/jid.2009.96

PubMed ID

  • 19387481

Additional Document Info

start page

  • 2451

end page

  • 62

volume

  • 129

number

  • 10