{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T18:51:53Z","timestamp":1787251913003,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573686"],"award-info":[{"award-number":["82573686"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a highly immunosuppressive cancer with limited treatment options and poor prognosis. Neutrophils, as prominent immune cells in the tumour microenvironment, critically shape disease progression and treatment response. Here, we aimed to identify pivotal neutrophil subsets driving HCC progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Neutrophil\u2010specific marker genes were identified through single\u2010cell RNA sequencing (scRNA\u2010seq) analyses. The clinical significance of neutrophils with triggering receptor expressed on myeloid cells\u20101 (TREM1) positive was assessed in HCC patient cohort by immunofluorescence staining. The immune landscape of HCC and the functional phenotype of TREM1+ neutrophils were further characterised using cytometry by time\u2010of\u2010flight (CyTOF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      scRNA\u2010seq analyses revealed that TREM1 was mainly expressed in intratumoural neutrophils within the HCC microenvironment. A high abundance of intratumoural TREM1\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils was significantly associated with poor prognosis in HCC patients. CyTOF profiling demonstrated that HCC tumours enriched with TREM1\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils exhibited CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell exclusion and increased infiltration of immunosuppressive macrophages. Moreover, TREM1\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils exhibited an immunosuppressive functional state. Pharmacological inhibition of TREM1 by VJDT enhanced the therapeutic efficacy of anti\u2010PD\u20101 antibody in HCC preclinical models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      TREM1 is mainly expressed in neutrophils in HCC and drives the immunosuppressive reprogramming of neutrophils and tumour microenvironment. Infiltration of TREM1\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils correlates with unfavourable clinical outcomes in HCC. Targeting TREM1 may augment the efficacy of anti\u2010PD\u20101 therapy in HCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70726","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T07:57:33Z","timestamp":1780646253000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>TREM1<\/scp>\n                    <sup>+<\/sup>\n                    Neutrophils Determine Immunosuppressive Microenvironment and Immunotherapy Response in Hepatocellular Carcinoma"],"prefix":"10.1111","volume":"46","author":[{"given":"Zhaowei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-1417","authenticated-orcid":false,"given":"Xiaobing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital  Zhengzhou 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