{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:44:41Z","timestamp":1789753481729,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The role of macrophages (Mo) and their prognostic impact in diffuse large B\u2010cell lymphomas (DLBCL) remain controversial. By regulating the lipid metabolism, Liver\u2010X\u2010Receptors (LXRs) control Mo polarization\/inflammatory response, and their pharmacological modulation is under clinical investigation to treat human cancers, including lymphomas. Herein, we surveyed the role of LXRs in DLBCL for prognostic purposes. Comparing bulk tumors with purified malignant and normal B\u2010cells, we found an intriguing association of\n                    <jats:italic>NR1H3<\/jats:italic>\n                    , encoding for the LXR\u2010\u03b1 isoform, with the tumor microenvironment (TME). CIBERSORTx\u2010based purification on large DLBCL datasets revealed a high expression of the receptor transcript in M1\u2010like pro\u2010inflammatory Mo. By determining an expression cut\u2010off of\n                    <jats:italic>NR1H3<\/jats:italic>\n                    , we used digital measurement to validate its prognostic capacity on two large independent on\u2010trial and real\u2010world cohorts. Independently of classical prognosticators,\n                    <jats:italic>NR1H3<\/jats:italic>\n                    <jats:sup>high<\/jats:sup>\n                    patients displayed longer survival compared with\n                    <jats:italic>NR1H3<\/jats:italic>\n                    <jats:sup>low<\/jats:sup>\n                    cases and a high\u2010resolution Mo GEP dissection suggested a remarkable transcriptional divergence between subgroups. Overall, our findings indicate\n                    <jats:italic>NR1H3<\/jats:italic>\n                    as a Mo\u2010related biomarker identifying patients at higher risk and prompt future preclinical studies investigating its mouldability for therapeutic purposes.\n                  <\/jats:p>","DOI":"10.1002\/hon.3050","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T18:43:45Z","timestamp":1658169825000},"page":"864-875","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<i>NR1H3<\/i>\n                    (LXR\u03b1) is associated with pro\u2010inflammatory macrophages, predicts survival and suggests potential therapeutic rationales in diffuse large b\u2010cell lymphoma"],"prefix":"10.1002","volume":"40","author":[{"given":"Maria Carmela","family":"Vegliante","sequence":"first","affiliation":[{"name":"Hematology and Cell Therapy Unit IRCCS\u2010Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saveria","family":"Mazzara","sequence":"additional","affiliation":[{"name":"Division of Hematopathology European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Maria","family":"Zaccaria","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Unit IRCCS\u2010Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"De Summa","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics and Pharmacogenetics Unit IRCCS\u2010Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Mathematics University of Bari Aldo Moro  Bari Italy"},{"name":"INDAM\u2010GNCS Research Group  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Melle","sequence":"additional","affiliation":[{"name":"Division of Hematopathology European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Motta","sequence":"additional","affiliation":[{"name":"Division of Hematopathology European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-2128","authenticated-orcid":false,"given":"Maria Rosaria","family":"Sapienza","sequence":"additional","affiliation":[{"name":"Division of Hematopathology European Institute of Oncology IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Opinto","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Unit IRCCS\u2010Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Volpe","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Unit IRCCS\u2010Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Bucci","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Unit IRCCS\u2010Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Gargano","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Unit IRCCS\u2010Istituto Tumori \u2018Giovanni Paolo II\u2019  Bari Italy"},{"name":"INDAM\u2010GNCS Research Group  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Enjuanes","sequence":"additional","affiliation":[{"name":"Unitat de Gen\u00f2mica Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Barcelona; 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