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Langerhans cells, immunomodulation and skin lesions. A quantitative, morphological and clinical study
1Department of Dermatology, University of Göteborg, Sweden.
Insights
Immunosuppression reduces epidermal Langerhans cells (LCs), increasing skin tumor risk, particularly with long-term triple therapy. LCs are also altered in basal cell carcinoma (BCC).
Area of Science:
- Immunodermatology
- Oncology
- Transplantation Immunology
Background:
- Epidermal Langerhans cells (LCs) are crucial for skin immunity, presenting antigens to T lymphocytes and potentially defending against skin tumors.
- Factors like aging, UV radiation, and immunosuppressive drugs can reduce LC numbers and function, potentially increasing skin cancer susceptibility.
- Understanding LC roles in immunosurveillance is vital for managing skin health in immunocompromised individuals.
Purpose of the Study:
- To investigate the importance of LCs in skin tumor immunosurveillance.
- To evaluate LC number and morphology in unaffected skin of patients with cutaneous tumors and in immunosuppressed patients.
- To examine LCs within basal cell carcinoma (BCC) and their association with inflammatory responses.
Main Methods:
- Analyzed LC populations using ATPase and CD1a staining.
- Assessed inflammatory response around BCC by quantifying HLA-DR+, CD3+, and ICAM-1+ cells.
- Studied skin tumor prevalence in renal transplant recipients on various immunosuppressive regimens (azathioprine, prednisolone, cyclosporin) using light and confocal laser scanning microscopy (CLSM).
Main Results:
- No significant difference in LC populations was found in patients treated with PUVA or those with skin tumors compared to controls; no age-related LC reduction was observed.
- Immunosuppressed patients, especially those on triple drug therapy (cyclosporin+azathioprine+prednisolone), showed reduced LC numbers.
- Long-term azathioprine and prednisolone treatment (10-25 years) correlated with a high prevalence of warts (40%) and skin tumors (29%), unlike shorter-term triple therapy.
- LCs in the epidermis overlying BCC were decreased in number and altered in morphology compared to perilesional skin; dermal LCs were noted around BCC nests.
Conclusions:
- The duration of immunosuppressive treatment is critical for the development of warts and skin tumors in transplant recipients.
- While immunosuppression reduces LC numbers, this reduction does not necessarily correlate with treatment duration or the presence of skin lesions.
- Alterations in epidermal LCs are associated with basal cell carcinoma, suggesting a role in tumor immunosurveillance.
Abstract:
The epidermal Langerhans cell (LC) plays an important role in contact hypersensitivity reactions by presenting the antigens to T lymphocytes. LCs may also play a role in defence mechanisms against neo-antigens in skin tumours. Some studies have indicated that the LC population declines with age. Ultraviolet radiation induces a significant reduction in the number of epidermal LCs and most immunosuppressive drugs decrease the number and function of LCs as well. Such alterations in LCs might predispose to the development of skin tumours. To evaluate the importance of LCs in immunosurveillance of skin tumours, the number and the morphology of LCs was investigated in unaffected skin of patients with cutaneous tumours and in immunosuppressed patients. LCs within basal cell carcinoma (BCC) were examined as well. ATPase and CD1a staining was used to visualise LCs. The inflammatory response around BCC was estimated by the expression of HLA-DR+, CD3+ and ICAM-1+ cells. The prevalence of skin tumours was studied in renal transplant recipients on different immunosuppressive treatments such as azathioprine (Aza) and prednisolone (P), cyclosporin (CyA), azathioprine and prednisolone or cyclosporin and prednisolone. We found no difference in LC populations in patients treated with PUVA (psoralen and UVA-radiation) or in patients with skin tumours as compared with controls and no age-related reduction in LC numbers. However, immunosuppressed patients showed a reduced number of LCs, especially those who had received triple drug therapy (CyA+Aza+P). Patients treated with azathioprine and prednisolone (10-25 years) had a high prevalence of multiple warts (40%) and skin tumours (29%). In contrast, warts and skin tumours were not common in patients treated for 5 years with CyA+Aza+P or with CyA+P. Thus, the duration of immunosuppressive treatment seems crucial for the development of warts and skin tumours. However, the reduction in LC numbers was not more pronounced with time or in patients with skin lesions as compared with those without lesions. In the epidermis overlying basal cell carcinoma (BCC) the number of LCs was decreased and their morphology changed as compared with LCs in perilesional skin. These alterations were documented in horizontal sheets as well as in vertical sections of the epidermis analysed by light microscopy and with confocal laser scanning microscopy (CLSM). The latter technique permits a quantitative and morphological analysis of LCs in the same tissue volume. In vertical sections, numerous LCs were observed in the dermis surrounding BCC nests.(ABSTRACT TRUNCATED AT 400 WORDS)