Regulation of immune-recognition molecules following delivery of plasmid backbone

Abstract Local intratumor delivery with electroporation of low levels plasmids encoding molecules, such as IL-12, IL-15, induces an antitumor effect without causing systemic toxicity. However, previous studies have predominately focused on the function delivered molecule encoded within plasmid, and ignored plasmid backbone. In this study, we found backbones pUMVC3 pVax1 induced up-regulation MHC class I (MHC-I), PD-L1, CD95 (Fas) CD155 tumor cell surface. These molecules participate in a considerable number immunoregulatory functions through their interactions activating inhibitory immune receptors. are well-known for role antigen (cross-) presentation, thereby functioning key players communication between cells cells. Increased PD-L1 expression is important monitor growth effectiveness inhibitor therapy. During cancer progression frequently downregulated, raising possibility that loss part mechanism evasion. Due to its prominent endogenous functions, has been gaining interest therapeutic target field immunology. Results from flow cytometry confirmed increased MHC-I PDL-1 B16F10, 4T1 KPC lines. Preliminary animal data tumor-bearing models, B16F10 melanoma, breast pancreatic mouse models showed was attenuated after intratumoral electroporation. Our also documented pSTAT1-NF-κB signaling pathway might be associated backbones’ up-regulating MHC-I, R01 CA186730