biostudies-literatureLi SNational Natural Science Foundation of China1883-1895https://www.ebi.ac.uk/biostudies/studies/S-EPMC12573374biostudies-literatureUnknown74(11)<h4>Background</h4>Current treatments with tyrosine kinase inhibitors and immune checkpoint inhibitors have limited efficacy for hepatocellular carcinoma (HCC) due to drug resistance. Emerging therapies such as chimeric antigen receptor T (CAR-T) and macrophage-based cell therapies are promising but need to be improved.<h4>Objectives</h4>This study investigates the role of macrophage NOD-like receptor family pyrin domain containing 6 (NLRP6) in HCC progression and its therapeutic potential.<h4>Design</h4>Immunofluorescence staining was performed in patient samples. Liver tumour models (autonomous, orthotopic, subcutaneous) were developed, and RNA sequencing, flow cytometry and immunohistochemistry were performed in wild-type, <i>Nlrp6</i> ^-/- mice, and cell-specific Nlrp6 knockoGutNLRP6 deficiency enhances macrophage-mediated phagocytosis via E-Syt1 to inhibit hepatocellular carcinoma progression.PMC1257337482272956Yu LLu YFu YLei GShi YLiu ZQian ZSafadi RZhang TLi SZhang XJia XHan JZha HfalseNLRP6 deficiency enhances macrophage-mediated phagocytosis via E-Syt1 to inhibit hepatocellular carcinoma progression.<h4>Background</h4>Current treatments with tyrosine kinase inhibitors and immune checkpoint inhibitors have limited efficacy for hepatocellular carcinoma (HCC) due to drug resistance. Emerging therapies such as chimeric antigen receptor T (CAR-T) and macrophage-based cell therapies are promising but need to be improved.<h4>Objectives</h4>This study investigates the role of macrophage NOD-like receptor family pyrin domain containing 6 (NLRP6) in HCC progression and its therapeutic potential.<h4>Design</h4>Immunofluorescence staining was performed in patient samples. Liver tumour models (autonomous, orthotopic, subcutaneous) were developed, and RNA sequencing, flow cytometry and immunohistochemistry were performed in wild-type, <i>Nlrp6</i> ^-/- mice, and cell-specific Nlrp6 knocko2025-01-01T00:00:00Z2025 Oct2026-06-05T09:43:59.459Z2026-05-15T03:12:00.214ZS-EPMC125733744047340110.1136/gutjnl-2024-334448