High numbers of DC-SIGN+ dendritic cells in lesional skin of cutaneous T-cell lymphoma

J Am Acad Dermatol. 2010 Jun;62(6):995-1004. doi: 10.1016/j.jaad.2009.06.082.

Abstract

Background: The role of dendritic cells (DCs) in disease progression of primary cutaneous T-cell lymphoma (CTCL) is not well understood. With their unique ability to induce primary immune responses as well as immunotolerance, DCs play a critical role in mediation of anti-tumor immune responses. Tumor-infiltrating DCs have been determined to represent important prognostic factors in a variety of human tumors.

Objective: To date, only circulating DC populations have been investigated in CTCL. Therefore we analyzed the expression and tissue distribution of different DC subset markers in lesional and nonlesional skin of patients with CTCL.

Methods: Twelve patients with mycosis fungoides or Sézary syndrome were included in the study. Tissue samples were obtained from lesional and nonlesional skin as a control. Immunohistochemistry was performed with different DC subset and regulatory T-cell markers and assessed using a digital image analysis system. Tissue distribution of DCs in relation to the tumor was analyzed by double immunofluorescence.

Results: We found a significant infiltration of CTCL lesions by immature CD209/DC-SIGN+ DCs with close contact to tumor cells. Matured and activated DCs were only rarely detected in lesions of CTCL.

Limitations: The sample size was small.

Conclusions: The preponderance of immature CD209/DC-DIGN+ DCs in contact with regulatory T cells in lesions of CTCL points to an important role of this subset in the host's immune reaction to the malignant T cells. Since these immature DCs are known to induce immunotolerance, they might play a role in the mediation of immune escape of the proliferating clone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / analysis
  • Cell Adhesion Molecules / metabolism*
  • Dendritic Cells / classification
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Fluorescent Antibody Technique
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Lectins, C-Type / metabolism*
  • Lymphoma, T-Cell, Cutaneous / immunology*
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Male
  • Middle Aged
  • Mycosis Fungoides / immunology
  • Mycosis Fungoides / pathology
  • Receptors, Cell Surface / metabolism*
  • Sezary Syndrome / immunology
  • Sezary Syndrome / pathology
  • Skin / immunology*
  • Skin / pathology
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antigens, CD
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Lectins, C-Type
  • Receptors, Cell Surface