The direct modulation of immune cells largely occurs in response to melanoma Exo-related inhibitory or pro-apoptotic signals and are mostly related to the exosomal expression of PD-L1 [32], while the indirect way involves the up-regulation of PD-1 by tumor accessory cells, such as mesenchymal stem cells (MSCs), which engulf the tumor microenvironment and restrain T-cell activation [33]. This evidence concerns the gene CD274 and neoplasm.