BCG emulsified in lipiodol expands epitopes to boost cancer immunotherapy

The application of Bacillus Calmette-Guerin (BCG) in tumor immunotherapy has great potential but faces challenges such as limited application scope and systemic infection risk. Here, we proposed lipiodol to deliver BCG and examined lipiodol-delivered BCG in several preclinical hepatocellular carcinoma (HCC) models. Lipiodol-delivered BCG can enter both types of cells, regardless of fibronectin expression, overcoming the limitations of BCG internalization dependent on affinity with fibronectin. Using lipiodol to deliver BCG for locoregional intervention of orthotopic liver tumors reduced tumor growth, reprogrammed tumor microenvironment, and enhanced signaling pathways related to antigen processing and presentation. Mechanistically, BCG peptides can be presented by MHC class I (MHC- I) on tumor cells and enhanced CD8+ T cell activity. BCG peptide single treatment or using lipiodol for delivery induced significant infiltration of CD8+T cells and dendritic cells (DCs) in tumor. Overall, this study demonstrated for the first time the potential of lipiodol-delivered BCG administration in treating liver tumors, highlighting its ability to enhance immune responses and augment BCG efficacy.