Abstract
The limited shared antigens identified in cancers are insufficient as targets for universal immunotherapy, and the impaired major histocompatibility complex class I (MHC-I) expression, limited antigen exposure, and deficiency of immunogenicity lead to tumors evading immune surveillance. Here, we proposed a facile and effective BCG emulsion immunotherapy strategy that expands antigen exposure, increasing immune recognition, and boosting cancer immunotherapy. BCG emulsion, exhibiting efficient internalization in a non-fibronectin-dependent manner, reduced tumor growth, reprogrammed tumor microenvironment, and enhanced signaling pathways related to antigen processing and presentation. BCG emulsion can reverse the MHC-I downregulation, and peptide fragments from BCG-derived molecules are presented on the tumor cell surface by MHC-I. CD8+ T cells recognize and are activated against these presented BCG epitopes identified by immunopeptideome. The BCG dominant epitope emulsion induced significant infiltration of CD8+T cells and dendritic cells in tumors. Overall, this study demonstrated for the first time the potential of BCG and BCG epitope administration in anti-cancer applications and provided new technological methods and ideas for cancer immunotherapy.

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