ABSTRACT
BACKGROUND: Langerhans cells (LCs) are professional Dendritic Cells (DCs) involved in immunoregulatory functions. At the skin level, LCs are immature. In response to tissue injuries, they migrate to regional Lymph Nodes (LNs), reaching a full maturation state. Then, they become effective antigen-presenting cells (APCs) that induce anti-cancer responses. Notably, melanoma patients present several DC alterations in the Sentinel Lymph Node (SLN), where primary antitumoral immunity is generated. LCs are the most represented DCs subset in melanoma SLNs and are expected to play a key role in the anti-melanoma response. With this paper, we aim to review the current knowledge and future perspectives regarding LCs and melanoma. METHODS: A systematic review was carried out according to the PRISMA statement using the PubMed (MEDLINE) library from January 2004 to January 2024, searching for original studies discussing LC in melanoma. RESULTS: The final synthesis included 15 articles. Several papers revealed significant LCs-melanoma interactions. CONCLUSIONS: Melanoma immune escape mechanisms include SLN LC alterations, favoring LN metastasis arrival/homing and melanoma proliferation. The SLN LCs of melanoma patients are defective but not irreversibly, and their function may be restored by appropriate stimuli. Thus, LCs represent a promising target for future immunotherapeutic strategies and cancer vaccines.