Matches in SemOpenAlex for { <https://semopenalex.org/work/W4376272026> ?p ?o ?g. }
- W4376272026 abstract "ABSTRACT Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. Here we establish a Patient-Derived Explant Culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+ T cell cytotoxic activity. We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax + metformin drug combination ex vivo , discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+ T cells and thus facilitating anti-tumor immunity. Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME." @default.
- W4376272026 created "2023-05-13" @default.
- W4376272026 creator A5008868111 @default.
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- W4376272026 date "2023-05-12" @default.
- W4376272026 modified "2023-10-16" @default.
- W4376272026 title "Respiratory Complex I Regulates Dendritic Cell Maturation in Explant Model of Human Tumor Immune Microenvironment" @default.
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