{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:47:42Z","timestamp":1793659662354,"version":"4.5.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Ovarian cancer (OC) is the most lethal gynecological malignancy. A deeper insight into tumor microenvironment (TME) interactions is essential for developing novel therapeutic approaches. leukocyte immunoglobulin-like receptor B4 (LILRB4) is a receptor involved in multiple biological and pathological processes in hematological malignancies; however, its role in the progression of solid tumors remains largely unexplored. In particular, the function within the OC is still unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically investigated the expression profile of LILRB4 in OC, along with its regulatory effects on OC cells, its role in immune cell modulation, and its potential as an immunotherapeutic target, using bioinformatics analyses,\n                      <jats:italic>in vitro<\/jats:italic>\n                      functional assays, and an\n                      <jats:italic>in vivo<\/jats:italic>\n                      orthotopic tumor model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that LILRB4 is the most highly expressed member of the LILRB family in OC, with significantly higher expression in tumor tissues than in normal ovarian tissues, and its elevated expression was associated with poor patient survival.\n                      <jats:italic>In vitro<\/jats:italic>\n                      functional assays demonstrated that LILRB4 knockdown significantly inhibited OC cell proliferation, migration, and invasion, whereas overexpression of LILRB4 promoted these malignant phenotypes. Further analyses revealed that LILRB4 expression was positively correlated with the infiltration of tumor-associated macrophages in the TME and promoted macrophage polarization toward the immunosuppressive M2c phenotype. Mechanistically,\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments showed that LILRB4 promoted tumor cell secretion of CCL5, activated the NF-\u03baB p65 signaling pathway, and enhanced M2c macrophage polarization, thereby promoting tumor progression and immune suppression. Finally, we demonstrated that downregulation of LILRB4 could enhance the sensitivity of OC to immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify LILRB4 as a key regulator of tumor progression and immune evasion in OC. High LILRB4 expression is associated with an immunosuppressive TME and poor response to immunotherapy, highlighting its potential as both a prognostic biomarker and a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1866073","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:41:05Z","timestamp":1785130865000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of LILRB4 as a regulator of M2c macrophages and a potential immunotherapeutic target in ovarian cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Huijuan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gynecology, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji 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