{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:51:18Z","timestamp":1790754678589,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Recent investigations have improved our understanding of the molecular aberrations supporting Waldenstr\u00f6m Macroglobulinemia (WM) biology; however, whether the immune microenvironment contributes to WM pathogenesis remains unanswered. We first showed how a transgenic murine model of human-like lymphoplasmacytic lymphoma\/WM exhibits an increased number of regulatory T (Treg) cells with respect to control mice. These findings were translated into the WM clinical setting, where the transcriptomic profiling of WM patients'-derived regulatory T cells (Tregs) unveiled a peculiar WM-devoted mRNA signature, with significant enrichment for NF-kB-mediated TNF-a signaling-, MAPK-, PI3K\/AKT-related genes; paralleled by different Treg functional phenotype. We demonstrated a significantly higher Treg-induction, -expansion and -proliferation triggered by WM cells as compared to their normal cellular counterpart; with a more profound effect within the context of CXCR4C1013G-mutated WM cells. By investigating the B-to-T cell cross-talk at single-cell level, we identified the CD40\/CD40-ligand as a potentially relevant axis supporting WM cell-Treg cell interaction. Our findings demonstrate the existence of a Treg-mediated immunosuppressive phenotype in WM, which can be therapeutically reversed by blocking the CD40L\/CD40 axis to inhibit WM cell growth.<\/jats:p>","DOI":"10.1182\/blood.2022019240","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T16:05:30Z","timestamp":1675440330000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":9,"title":["Targeting the immune microenvironment in Waldenstr\u00f6m Macroglobulinemia via halting the CD40\/CD40-ligand axis"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-9416","authenticated-orcid":false,"given":"Antonio","family":"Sacco","sequence":"first","affiliation":[{"name":"ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Desantis","sequence":"additional","affiliation":[{"name":"University of Bari Medical School, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2017-4206","authenticated-orcid":false,"given":"Jon","family":"Celay","sequence":"additional","affiliation":[{"name":"University of Navarra, Pamplona, Spain, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Giustini","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Rigali","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-0935","authenticated-orcid":false,"given":"Francesco D","family":"Savino","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili di Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1530-6729","authenticated-orcid":false,"suffix":"Prof","given":"Michele","family":"Cea","sequence":"additional","affiliation":[{"name":"University of Genoa, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Soncini","sequence":"additional","affiliation":[{"name":"University of Genoa, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Cagnetta","sequence":"additional","affiliation":[{"name":"University of Genoa, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Giovanni","family":"Solimando","sequence":"additional","affiliation":[{"name":"University of Bari Medical School, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"D'Aliberti","sequence":"additional","affiliation":[{"name":"University of Milano-Bicocca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8130-5954","authenticated-orcid":false,"given":"Silvia","family":"Spinelli","sequence":"additional","affiliation":[{"name":"University of Milano-Bicocca, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6087-2666","authenticated-orcid":false,"given":"Daniele","family":"Ramazzotti","sequence":"additional","affiliation":[{"name":"University of Milano - Bicocca, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-2569","authenticated-orcid":false,"given":"Camillo","family":"Almici","sequence":"additional","affiliation":[{"name":"Centro Manipolazione e Criopreservazione Cellule Staminali, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Todoerti","sequence":"additional","affiliation":[{"name":"Fondazione C\u00e0 Granda IRCCS Policlinico, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Dr","given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Anastasia","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3052-7463","authenticated-orcid":false,"given":"Alessandra","family":"Tucci","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"MD","given":"Marina","family":"Motta","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili di Brescia, Lombardia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1000-0461","authenticated-orcid":false,"given":"Marco","family":"Chiarini","sequence":"additional","affiliation":[{"name":"Clinical Chemistry Laboratory, Flow Cytometry Section, ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8269-440X","authenticated-orcid":false,"given":"Yawara","family":"Kawano","sequence":"additional","affiliation":[{"name":"Kumamoto University Hospital, Kumamoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Al","family":"Martinez-Climent","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-9620","authenticated-orcid":false,"given":"Rocco","family":"Piazza","sequence":"additional","affiliation":[{"name":"University of Milano - Bicocca, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-5128","authenticated-orcid":false,"given":"Aldo M","family":"Roccaro","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2023,2,3]]},"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2022019240\/2032584\/blood.2022019240.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2022019240\/2032584\/blood.2022019240.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T16:05:32Z","timestamp":1675440332000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2022019240\/494349\/Targeting-the-immune-microenvironment-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2022019240","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]},"article-number":"blood.2022019240"}}