Figure 1. The immunological scenario in electrochemotherapy treated melanoma metastases. A schematic representation of electrochemotherapy (ECT) treatment is shown: the electrode inserted in the subcutaneous melanoma metastasis (MTX) after bleomycin administration induces tumor cell electroporation. This results in massive tumor cell death with the release of tumor-associated antigens (TAA) and mitigation of the immunosuppressive microenvironment. These TAAs are captured by different dendritic cell (DC) subsets—Langerhans cells (LCs), dermal DCs (dDCs), plasmacytoid DCs (pDCs)—that migrate to draining lymph nodes and present them to tumor-specific T cells. The combination of ECT with DC-targeting adjuvants and/or with the inhibition of immunosuppressive factors might lead to an effective systemic anti-melanoma immunity, accompanied by the regression of untreated distant metastases.