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Exploiting BCG's recognized immune\u2010boosting properties, preclinical trials are conducted using HCC mice, with a single subcutaneous dose of BCG administered post\u2010tumor formation. Results indicate that BCG treatment effectively diminishes tumor burden and extends survival in both male and female HCC mice. Positive influences on hepatic fibrosis and metabolism are observed, leading to a reduction in lipid levels. Spatial analysis underscores BCG's tumor\u2010specific effects, inducing the enrichment of metabolic pathways and inhibiting various cancer\u2010related pathways. Furthermore, BCG promotes immune cell infiltration, including CD4+, CD8+ T cells, and M1 macrophages, in both v\u2010akt murine thymoma viral oncogene homolog 1(AKT)\/neutoblastoma RAS viral oncogene homolog (RAS) and \u03b2\u2010catenin positive HCC models. Interestingly, blocking T cells, trained immunity, and Interferon\u2010\u03b3 (IFN\u2010\u03b3) function reverses BCG's anti\u2010HCC effects. In conclusion, BCG emerges as a promising treatment option for HCC, characterized by a favorable safety profile and efficacy in inhibiting fibrosis, improving metabolism, and engaging both trained immunity and T cells in therapeutic mechanisms.<\/jats:p>","DOI":"10.1002\/advs.202308242","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T23:01:36Z","timestamp":1706914896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["BCG as an Innovative Option for HCC Treatment: Repurposing and Mechanistic Insights"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7788-2548","authenticated-orcid":false,"given":"Farzam","family":"Vaziri","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California Davis Health  Sacramento CA 95817 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