In the clinical treatment of metastatic melanoma and bladder tumors, there is an adenovirus-based CD40 ligand (AdCD40L) gene therapy in which CD40L interacts with CD40 to promote an adjuvant T-cell 1 (Th1) immune response, leading to T-cell activation and migration to the TME [4, 119, 120]. This evidence concerns the gene CD40LG and metastatic melanoma.