A new era in melanoma immunotherapy: focus on DCs metabolic reprogramming.

Melanoma, being one of the most dangerous forms of skin cancer, is characterized by its aggressive and metastatic nature, with the potential to develop resistance to various treatments. This resistance makes the disease challenging to treat, emphasizing the need for new treatment strategies. Within the tumor microenvironment (TME), melanoma cells exploit metabolic shifts, particularly glycolysis, to create an immunosuppressive TME that prevents dendritic cells (DCs) from functioning properly. Essential metabolic alterations such as lactate and lipid accumulation, and lack of tryptophan disrupt DC maturation, antigen presentation, and T cell activation. In recent years, melanoma immunotherapy has increasingly focused on reprogramming the metabolism of DCs. This review paper aims to provide insights into the metabolic suppression of melanoma-associated DCs, allowing the design of therapeutic strategies based on metabolic interventions to promote or restore DC function. This contribution reviews the metabolic reprogramming of DCs as a new approach for melanoma immunotherapy.