{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:23:18Z","timestamp":1787638998128,"version":"build-2736575974"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"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>In multiple myeloma (MM), the immune system is disrupted, partly due to tumor-modified bone marrow mesenchymal stromal cells (BM-MSCs). These MSCs show altered glycosylation, including increased sialylation, which may promote immune evasion through Siglec interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We quantified sialic acids and Siglec ligands on healthy donors-, MM-, T-MM-(treated multiple myeloma) and MGUS (monoclonal gammopathy of undetermined significance)-MSCs, and examined how different culture conditions (myeloma coculture, conditioned medium, hypoxia, inflammation, 3D culture) affect MSC glycosylation. Expression of 84 glycosylation-related genes was screened by qPCR. Macrophage polarization was then assessed after modulating MSC sialylation using inhibitors or an activator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MM-MSCs exhibited significantly higher surface sialylation than HD-, T-MM-, and MGUS-MSCs. MM-MSC sialylation was positively correlated with the percentage of plasma cells and the LDH levels of MM patients. Direct MSC-plasma cell cocultures further enhanced hypersialylation compared with conditioned medium or transwell coculture, indicating a contact-dependent mechanism. qPCR screening identified two dysregulated genes, ST6Gal1 and NEU2, implicated in the sialylation pathway. Inflammation and hypoxia appeared as key players in the expression of Siglec-7L, Siglec-9L and ST6Gal1 by MSCs. Functionally, we showed that increased sialylation promoted an M2-like phenotype as measured by CD206, whereas inhibition shifted macrophages toward an M1-like profile as measured by CD40 and HLA-DR. We also showed that when MSC sialylation is inhibited, their ability to induce an M2 phenotype is reduced, as evidenced by the lower production of M2-associated cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that BM-MSC hypersialylation may contribute to immune remodeling in MM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1919303","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:36:24Z","timestamp":1787636184000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced sialylation of bone marrow mesenchymal stromal cells contributes to immune remodeling through macrophage polarization in multiple myeloma 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Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Meuleman","sequence":"additional","affiliation":[{"name":"Translational Hematology and Oncology Research Laboratory, Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles (ULB)","place":["Brussels, Belgium"]},{"name":"Department of Hematology, Jules Bordet Institute","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Lagneaux","sequence":"additional","affiliation":[{"name":"Translational Hematology and Oncology Research Laboratory, Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles (ULB)","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basile","family":"Stamatopoulos","sequence":"additional","affiliation":[{"name":"Translational Hematology and Oncology Research Laboratory, Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles (ULB)","place":["Brussels, 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