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Review
. 2010 Dec;31(12):460-6.
doi: 10.1016/j.it.2010.10.001. Epub 2010 Nov 9.

The contribution of Langerhans cells to cutaneous malignancy

Julia Lewis  1 , Renata Filler, Debra A Smith, Kseniya Golubets, Michael Girardi
Affiliations
Review

The contribution of Langerhans cells to cutaneous malignancy

Julia Lewis et al. Trends Immunol. 2010 Dec.

Abstract

The skin is at the forefront of environmental exposures, such as ultraviolet radiation and a myriad of chemicals, and is at risk for malignant transformation. The skin is a highly responsive immunological organ that contains a unique population of immature intraepidermal dendritic cells (DCs) called Langerhans cells (LCs). Although LCs show morphological and migratory changes in response to epidermal perturbation, and can function as antigen-presenting cells to activate T cells, their role in carcinogenesis is unknown. Here we review recent studies that have provided clues to the potential roles that LCs might play in the pathogenesis of skin cancer, beyond their stimulation or regulation of adaptive immunity. Understanding this role of LCs might provide new perspectives on the relevance of DC populations that are resident within other epithelial tissues for cancer.

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Figures

Figure 1
Figure 1. LC dendritic processes might extend superficially to the sub-stratum corneum
Suprabasal LCs might extend their dendritic processes superficially, through claudin-1-containing tight junctions, to just below the stratum corneum [13]. This occurs most notably after epidermal perturbation or cytokine activation. These LC dendritic tips appear to have endocytic capabilities, and might represent a potential entry for chemical mutagens into the basal skin and draining lymph nodes.
Figure 2
Figure 2. Hypothetical model of the spectrum of potential pro-tumor influences of LCs on cutaneous chemical carcinogenesis
LCs could contribute to initiation of mutagenesis by internalizing and metabolizing PAHs to increase mutagenicity, or by serving as a depot or relay station for mutagens [20]. The proximity of LCs to basal keratinocytes raises speculation for other pro-tumor influences of LCs, for example, facilitating survival and/or providing a growth advantage to any genetically altered keratinocytes, or by preventing antitumor immunity, through production of growth factors or cytokines. KC: keratinocyte.
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