The neuropeptide alpha-melanocyte-stimulating hormone is critically involved in the development of cytotoxic CD8+ T cells in mice and humans.

BACKGROUND: The neuropeptide alpha-melanocyte-stimulating hormone is well known as a mediator of skin pigmentation. More recently, it has been shown that alpha-melanocyte-stimulating hormone also plays pivotal roles in energy homeostasis, sexual function, and inflammation or immunomodulation. Alpha-melanocyte-stimulating hormone exerts its antiinflammatory and immunomodulatory effects by binding to the melanocortin-1 receptor, and since T cells are important effectors during immune responses, we investigated the effects of alpha-melanocyte-stimulating hormone on T cell function. METHODOLOGY/PRINCIPAL FINDINGS: T cells were treated with alpha-melanocyte-stimulating hormone, and subsequently, their phenotype and function was analyzed in a contact allergy as well as a melanoma model. Furthermore, the relevance of alpha-melanocyte-stimulating hormone-mediated signaling for the induction of cytotoxicity was assessed in CD8(+) T cells from melanoma patients with functional and nonfunctional melanocortin-1 receptors. Here we demonstrate that the melanocortin-1 receptor is expressed by murine as well as human CD8(+) T cells, and we furthermore show that alpha-melanocyte-stimulating hormone/melanocortin-1 receptor-mediated signaling is critical for the induction of cytotoxicity in human and murine CD8(+) T cells. Upon adoptive transfer, alpha-melanocyte-stimulating hormone-treated murine CD8(+) T cells significantly reduced contact allergy responses in recipient mice. Additionally, the presented data indicate that alpha-melanocyte-stimulating hormone via signaling through a functional melanocortin-1 receptor augmented antitumoral immunity by up-regulating the expression of cytotoxic genes and enhancing the cytolytic activity in tumor-specific CD8(+) T cells. CONCLUSIONS/SIGNIFICANCE: Together, these results point to an important role of alpha-melanocyte-stimulating hormone in MHC class I-restricted cytotoxicity. Therefore, treatment of contact allergies or skin cancer with alpha-melanocyte-stimulating hormone or other more stable agonists of melanocortin-1 receptor might ameliorate disease or improve antitumoral immune responses.

Eczematous malignant melanoma: a wolf in sheep's clothing.

BACKGROUND: The clinical diagnosis of amelanotic melanoma is still a challenge. CASE REPORT: A 72-year-old patient was first referred to us for the excision of a melanoma of the chin. In the first examination, we discovered another melanoma of the trunk. Both malignancies were excised and histopathology confirmed the clinical diagnosis of melanomas with Clark level II and III, respectively. Apart from these melanomas, physical examination revealed an 8 cm x 5 cm large erythematous plaque on the left upper arm. We first thought of a common eczema or a superficial mycosis; a cutaneous T cell lymphoma (CTCL) was considered as well. Surprisingly, the pathology report showed typical features of a malignant melanoma. The diagnosis was confirmed by 3 further punch biopsies (Clark level III, Breslow 0.6 mm). The lesion was excised with 1-cm safety margins. CONCLUSIONS: Amelanotic melanoma may appear as an erythematous macula or plaque; clinical symptoms are erythema, edema, pruritus or a slow increase in size and hypopigmentation or discoloration. Only a biopsy can determine the etiology of a non-specific lesion.