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Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Identification and characterization of pDC-like cells in normal mouse skin and melanomas treated with imiquimod
Francesca Palamara1, Simone Meindl, Martin Holcmann
1Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Austria.
Insights
Topical imiquimod treatment recruits plasmacytoid dendritic cells (pDCs) to the skin, potentially mediating antitumor effects. Activating these pDCs may offer a novel cancer immunotherapy approach.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Normal skin harbors Langerhans cells and dermal dendritic cells (DCs).
- Plasmacytoid DCs (pDCs) are a distinct subset of DCs found in lymphoid organs.
Purpose of the Study:
- To identify and characterize a novel DC population in imiquimod-treated mouse skin.
- To investigate the role of this DC population in the antitumor effects of imiquimod.
Main Methods:
- Topical application of imiquimod to mice.
- Flow cytometry analysis of skin and spleen cells.
- Induction of intradermal melanomas in mice.
Main Results:
- A population of CD4(+)CD3(-) pDC-like cells accumulated in the dermis and spleen after imiquimod treatment.
- These cells expressed markers consistent with pDCs and were found in both normal skin and melanomas.
- Imiquimod treatment led to tumor regression, and the number of pDCs correlated with the clinical response.
Conclusions:
- Imiquimod treatment recruits pDC-like cells to the skin, suggesting their involvement in antitumor activity.
- Targeting and activating these pDCs could be a promising strategy for cancer immunotherapy.
Abstract:
Among the different subsets of dendritic cells (DC) described in humans and mice, epidermal Langerhans cells and dermal DCs represent the only DC populations resident in normal skin. In this study we describe a population of CD4(+)CD3(-) plasmacytoid DC (pDC)-like cells that accumulate in the dermis and spleens of mice topically treated with imiquimod, a low m.w. immune response modifier with potent antiviral and antitumor activities. These CD4(+)CD3(-) cells coexpress GR-1, B220, MHC class II, and, to a lesser extent, CD11c and display the phenotypic features of pDCs described in lymphoid organs. The accumulation of pDC-like cells after imiquimod treatment was detected not only in normal skin, but also in intradermally induced melanomas. Imiquimod treatment leads either to complete regression or to a significant reduction of the tumors. The number of pDCs correlates well with the clinical response of the tumors to the drug, suggesting that the antitumor effects of imiquimod could be mediated at least in part by the recruitment of pDC-like cells to the skin. Therefore, strategies aimed at activating and directing these cells into neoplastic tissues may be a promising and novel approach for the immunotherapy of various types of cancer.

