Decreased density of epidermal dendritic cells in melanocytic naevi: the possible role of in vivo sun exposure.

Melanocytic naevi are benign skin tumours that originate in the epidermis. The pathogenesis of naevi and cutaneous malignant melanoma has been linked to sun exposure. This study evaluates alterations in the density of immunologically active epidermal dendritic cells (EDCs) in naevi in response to sun exposure. Immunohistologically stained sections of 266 naevi from patients from Israel (n=135) and Germany (n=131) were evaluated. The proportion of naevi with decreased density of HLA-DR+ (dDR+) and CD1a+ (dCD1a+) EDCs was analysed according to country, last exposure to sunlight, anatomical location and histological subtype. The risk of dDR+ was found to be linked to residence in Israel compared with Germany (odds ratio [OR] = 4.2; 95% confidence interval [CI] = 2.0-8.9), suggesting a latitude-dependent effect. Naevi removed in summer had a higher risk of dCD1a+ (OR = 4.7; 95% CI = 2.3-9.8) compared with those removed in winter. The most conspicuous dDR+ among the German cases, and dCD1a+ among the Israelis, occurred in naevi located on commonly exposed skin. The similar densities of EDCs in the lesional and perilesional skin of the majority of the naevi indicates that the underlying naevus cells have no effect on EDC density. It is not unlikely that an altered immune response due to dDR+ and dCD1a+ in sun-exposed skin in the vicinity of naevi contributes to the subsequent melanoma risk in highly susceptible individuals.

[Immunochemotherapy of malignant melanoma. Epifocal administration of dinitrochlorobenzene (DNCB) combined with systemic chemotherapy with dacarbazine (DTIC)]. / Immunchemotherapie des malignen Melanoms. Epifokale Applikation von Dinitrochlorbenzol (DNCB) kombiniert mit systemischer Chemotherapie mit Dacarbacin (DTIC).

We describe an immunochemotherapy for metastatic melanoma that combines epifocal applications of the contact sensitizer DNCB over cutaneous metastases with systemic DTIC treatment. 4 complete remissions and 3 partial remissions were achieved in 15 patients. 6 of these remissions were seen in the 7 previously untreated patients. The advantages of this therapy which is in particular interesting for dermatologists are tolerable side effects and low costs. This publication is designed to stimulate larger randomized trials in order to answer open questions.

Interleukin-10 production in malignant melanoma: preferential detection of IL-10-secreting tumor cells in metastatic lesions.

IL-10 mRNA expression and protein production in established melanoma cell lines and freshly cultured primary and metastatic melanoma cells was examined. The in situ distribution of IL-10 in native melanoma tissue was also investigated by immunohistochemistry in primary tumors, metastases, benign melanocytic nevi and normal skin of healthy persons and melanoma patients. IL-10 mRNA, but not IL-10 protein in the culture supernatant, was found in 1 of 4 cultured melanoma cells of primary tumors, while 3 of 6 melanoma-metastasis-derived cultures expressed both IL-10 mRNA and protein. No IL-10 was detected in skin biopsies of healthy volunteers or in the healthy skin of melanoma patients; nor was IL-10 found in congenital melanocytic nevi. In only 1 of the 11 examined primary malignant melanomas was IL-10 immunoreactivity detected within the cytoplasm of cells in the tumor. On the other hand, 4 of 9 metastases clearly displayed scattered IL-1O+ cells. In all sections with IL-10-positive cells, the cells were positive for HMB-45. No co-expression of CD3 and IL-10 was observed. The data suggest that melanoma cells themselves are the main origin of IL-10 in tumor specimens in vivo. The preferential expression of IL-10 in metastatic lesions and in cultured cells from metastases might indicate an increased spreading potential of IL-10-secreting melanoma-cell clones.

Elevated serum levels of interleukin-10 in patients with metastatic malignant melanoma.

Interleukin-10 (IL-10), originally described as a product of TH2 cell clones, has been recognized as a potential immunosuppressive cytokine. To investigate the relevance of IL-10 in melanoma patients in vivo, we studied IL-10 serum levels in 104 untreated patients in different stages of the disease; 20 healthy subjects and 22 patients with inflammatory dermatoses served as controls. Serum levels were measured by ELISA. Only one of 31 patients with stage I melanoma (3%) and one of 16 stage II patients (6%) showed detectable IL-10 levels. Interestingly, six of 17 patients with lymph node metastases (stage III, 35%) and 29 of 40 patients with widespread disease (stage IV, 73%) revealed IL-10 levels of 15-480 pg/ml. No healthy person and only one control patient had a detectable IL-10 serum level. The data suggest that IL-10 in melanoma patients may contribute to down-modulation of anti-tumour responses in vivo.