Interaction between Merkel cell carcinoma and the immune system: Pathogenetic and therapeutic implications.

Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma. It usually appears on the face and neck of elderly Caucasian people as a flesh-colored, erythematous or violaceous dome-shaped, non-tender nodule with a smooth surface. In immunocompromised patients with T-cell dysfunction, such as patients with acquired immunodeficiency syndrome (AIDS) or solid organ transplant recipients, the incidence of this disease is markedly increased. This suggests a link between the development of MCC and the immune system. Merkel cell polyolmavirus (MCPyV) is clonally integrated into the majority of MCCs, suggesting its causative role in the pathogenesis of the majority of these tumors. Despite wide local excision, sentinel lymph node biopsy, and eventually, adjuvant radiation therapy, which remains the first-line treatment for MCC, the identification of MCPyV has opened novel therapeutic insights. Novel therapeutic strategies could be to inhibit MCPyV oncoproteins and to stimulate immune responses against virus-infected tumor cells by immunostimulatory cytokines, including interferons and interleukin-2.

Toll-like receptors and cutaneous melanoma.

Innate immune cells recognize highly conserved pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). Previous studies have demonstrated that PRRs also recognize endogenous molecules, termed damage-associated molecular patterns (DAMPs) that are derived from damaged cells. PRRs include Toll-like receptors (TLRs), scavenger receptors, C-type lectin receptors and nucleotide oligomerization domain-like receptors. To date, 10 TLRs have been identified in humans and each receptor responds to a different ligand. The recognition of PAMPS or DAMPs by TLRs leads to the activation of signaling pathways and cellular responses with subsequent pro-inflammatory cytokine release, phagocytosis and antigen presentation. In the human skin, TLRs are expressed by keratinocytes and melanocytes: The main cells from which skin cancers arise. TLRs 1-6 and 9 are expressed in keratinocytes, while TLRs 2-5, 7, 9 and 10 have been identified in melanocytes. It is hypothesized that TLRs may present a target for melanoma therapies. In this review, the involvement of TLRs in the pathogenesis and treatment of melanoma was discussed.