biostudies-literatureLi QThe Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher LearningInnovative Research Team of High-level Local University in ShanghaiNational Natural Science Foundation of ChinaShanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant SupportTwo-hundred Talents” Program of Shanghai Jiao Tong University School of Medicinee008917https://www.ebi.ac.uk/biostudies/studies/S-EPMC11328658biostudies-literatureUnknown12(6)<h4>Background and aims</h4>The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy.<h4>Methods</h4>De novo <i>MYC/Trp53^-/-</i> liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underlJournal for immunotherapy of cancerProtein O-fucosyltransferase 1 promotes PD-L1 stability to drive immune evasion and directs liver cancer to immunotherapy.PMC11328658N/A20221704 to Y.L.82073190 and 82272684 to Y.L.TP2022054 to Y.L.SHSMU-ZLCX20211602 to Q.X.Liu YQian YLi SZhu ZGuo WXia QWang FLi QTong YLi LfalseProtein O-fucosyltransferase 1 promotes PD-L1 stability to drive immune evasion and directs liver cancer to immunotherapy.<h4>Background and aims</h4>The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy.<h4>Methods</h4>De novo <i>MYC/Trp53^-/-</i> liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underl2024-01-01T00:00:00Z2024 Jun2025-04-19T20:41:31.747Z2025-04-19T20:41:31.747ZS-EPMC113286583890885410.1136/jitc-2024-008917