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• W4386709737 abstract "Abstract The durable response rate to immune checkpoint blockade such as anti-programmed cell death-1 (PD-1) antibody remains relatively low in hepatocellular carcinoma (HCC), mainly depending on an immunosuppressive microenvironment with limited number of CD8 + T cells, especially stem-like CD8 + T cells, in tumor tissues. Here we develop engineered microparticles (MPs) derived from alpha-fetoprotein (AFP)-overexpressing macrophages to load resiquimod (R848@M2pep-MPs AFP ) for enhanced anti-PD-1 therapy in HCC. R848@M2pep-MPs AFP target and reprogram immunosuppressive M2-like tumor-associated macrophages (TAMs) into M1-like phenotype. Meanwhile, R848@M2pep-MPs AFP -reprogrammed TAMs act as antigen-presenting cells, not only presenting AFP antigen to activate CD8 + T cell-mediated antitumor immunity, but also providing an intra-tumoral niche to maintain and differentiate stem-like CD8 + T cells. Combination immunotherapy with anti-PD-1 antibody generates strong antitumor immune memory and induces abundant stem-like CD8 + T cell proliferation and differentiation to terminally exhausted CD8 + T cells for long-term immune surveillance in orthotopic and autochthonous HCC preclinical models in male mice. We also show that the R848-loaded engineered MPs derived from macrophages overexpressing a model antigen ovalbumin (OVA) can improve anti-PD-1 therapy in melanoma B16-OVA tumor-bearing mice. Our work presents a facile and generic strategy for personalized cancer immunotherapy to boost anti-PD-1 therapy." @default.
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• W4386709737 date "2023-09-13" @default.
• W4386709737 modified "2023-10-14" @default.
• W4386709737 title "Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy" @default.
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• W4386709737 doi "https://doi.org/10.1038/s41467-023-41438-9" @default.
• W4386709737 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37704614" @default.
• W4386709737 hasPublicationYear "2023" @default.
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