Langerhans cells in premalignant and malignant skin diseases

Abstract

The skin is the largest organ of the body and has many different functions. The epidermis as the most superficial layer of the skin forms the first barrier of protection from invasion of foreign substances into the body. The skin is an essential part of the immune system. Immune cells of the epidermis and dermis participate in the defence against pathogens, in particular through T lymphocytes in transit, tissue macrophages and a network of cutaneous dendritic cells (DCs), which are key for perception of danger and initiating both innate and adaptive protective responses (I). DCs are antigen-presenting cells derived from the hematopoietic stem cell (2). LCs are the DCs of the epidermis (3). Skin resident LCs are well characterized and regarded as typical immature DCs. The identification of antigen, and the subsequent activation and migration of LCs towards the draining lymph nodes are well-studied processes (4). It is quite remarkable that, as early as 1868. Paul Langerhans discovered the stellate-shaped epidermal cells that now bear his name (5). However, 100 years were subsequently needed to establish the fact that LCs are potent antigen-presenting cells appertaining to the leukocyte system (6). In parallel, the pioneering work of Steinman and Cohn leading to the identification of splenic DCs (7) formed the basis for connecting LCs to the emerging DCs system. One common feature of DCs is their amazing faculty to present protein-derived peptide antigens to naive T lymphocytes (8). LC constituents of the skin immune system, are a network of dendritic major histocompatibility complex (MHC) class II antigen-presenting cells involved in initiation of cutaneous immune responses (9). LCs are important for presentation tumour-associated antigens. Probably they are integral in host resistance against malignant neoplasms that emerge in the epidermis. Local or distant progression of a malignant tumour is critically important for further destiny of patients. It is influenced by many factors dependent on the biological behaviour of tumour cells. The question of failure of the immune defence, where antigen presentation is a key component, must also be assessed. Whether LCs in tumour act the same way as LCs in normal tissues or whether the tumours injure LCs phenotype and function remains unknown (10). LCs have been studied in a variety of cancers ( 11-16). However, despite the significant amount of investigation in the past few years, a function of LCs in skin tumours is only partially known.Squamous cell carcinoma (SCC) is relatively common skin tumour which if untreated, generally has a progressive clinical course with development of metastatic disease and often lethal outcome (17). With invasive SCC, masses of malignant kératinocytes extend through the basement membrane demonstrating different levels of atypia ranging from well differentiated to anaplastic. Having crossed over into the dermis they can metastasize.Actinic keratosis (AK). also known as solar or senile keratosis is by far the most common precancerous dermatos...

Basal Cell Carcinoma in Xeroderma Pigmentosa: Reduced CD1a Expression as a Sensitive Predictor of Recurrence

“…These data explain the results proven in the present study in which the LCs count at the 3 different areas (intratumoral, peritumoral, and perilesional epidermis) were of significantly lower mean values in XP patients compared with non-XP controls. To our knowledge, LC count was not investigated before in BCC of XP patients; however, it was reported to be of lower density with morphologic changes in the BCC lesions of normal individuals compared with normal skin 9,11,22–25…”

“…To our knowledge, LC count was not investigated before in BCC of XP patients; however, it was reported to be of lower density with morphologic changes in the BCC lesions of normal individuals compared with normal skin. 9,11,[22][23][24][25] Furthermore, UV exposure not only affects the LCs numbers but also affects their antigen-presenting capacity. UV-irradiated LCs present antigens to Th2 cells, but fail to activate Th1 cells.…”

Distribuição das células dendríticas em sarcoma de Kaposi oral associado à AIDS

“…LC are bone marrow derived DC found in the epithelium of normal skin and mucosas that encounter invading foreign pathogens in these surfaces, transfer to connective tissue where they are known as IDC and move toward regional lymph nodes where antigens are presented to naïve T lymphocytes 8 . There is a growing number of evidences supporting the hypothesis that different subtypes of DC play important roles in the immunosurveillance against neoplastic cells and that the distribution and/or the regular function of these cellular populations are altered in many human tumors including oral cancer, lip cancer, mycosis fungoids, cutaneous squamous cell carcinomas, and others [8][9][10][11] . Moreover, different authors have attributed a significant prognostic importance for DC in several of these malignant neoplasms 12,13 , speculating that changes in these cells would not only predispose to neoplastic development, but it would also represent potential therapeutic targets for future chemotherapy schemes.…”