{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:26:29Z","timestamp":1793499989802,"version":"4.5.0"},"reference-count":49,"publisher":"American Society of Hematology","issue":"12","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,19]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>The promising results obtained with immunotherapeutic approaches for multiple myeloma (MM) call for a better stratification of patients based on immune components. The most pressing being cytotoxic lymphocytes such as natural killer (NK) cells that are mandatory for MM surveillance and therapy. Here, we performed a single-cell RNA sequencing analysis of NK cells from 10 patients with MM and 10 age\/sex\u2013matched healthy donors that revealed important transcriptomic changes in the NK cell landscape affecting both the bone marrow (BM) and peripheral blood compartment. The frequency of mature cytotoxic CD56dim NK cell subsets was reduced in patients with MM at the advantage of late-stage NK cell subsets expressing NF-\u03baB and interferon-I inflammatory signatures. These NK cell subsets accumulating in patients with MM were characterized by low CD16 and CD226 expression and poor cytotoxic functions. MM CD16\/CD226Lo NK cells also had adhesion defects with reduced lymphocyte function-associated antigen 1 (LFA-1) integrin activation and actin polymerization that may account for their limited effector functions in\u00a0vitro. Finally, analysis of BM-infiltrating NK cells in a retrospective cohort of 177 patients with MM from the Intergroupe Francophone du My\u00e9lome (IFM) 2009 trial demonstrated that a high frequency of NK cells and their low CD16 and CD226 expression were associated with a shorter overall survival. Thus, CD16\/CD226Lo NK cells with reduced effector functions accumulate along MM development and negatively affect patients\u2019 clinical outcomes. Given the growing interest in harnessing NK cells to treat myeloma, this improved knowledge around MM\u2013associated NK cell dysfunction will stimulate the development of more efficient immunotherapeutic drugs against MM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023023529","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T19:59:46Z","timestamp":1718395186000},"page":"1271-1283","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["NK cells with adhesion defects and reduced cytotoxic functions are associated with a poor prognosis in multiple myeloma"],"prefix":"10.1182","volume":"144","author":[{"given":"Eve","family":"Blanquart","sequence":"first","affiliation":[{"name":"1Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6737-7281","authenticated-orcid":false,"given":"R\u00fc\u00e7han","family":"Ekren","sequence":"additional","affiliation":[{"name":"1Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6338-6986","authenticated-orcid":false,"given":"Bineta","family":"Rigaud","sequence":"additional","affiliation":[{"name":"1Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-4345","authenticated-orcid":false,"given":"Marie-V\u00e9ronique","family":"Joubert","sequence":"additional","affiliation":[{"name":"1Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"},{"name":"2Institut Universitaire du Cancer, Centre hospitalier universitaire de Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1313-2857","authenticated-orcid":false,"given":"Virginie","family":"Baylot","sequence":"additional","affiliation":[{"name":"1Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"},{"name":"2Institut Universitaire du Cancer, Centre hospitalier universitaire de Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Daunes","sequence":"additional","affiliation":[{"name":"1Cancer Research Center of Toulouse, INSERM, Centre National de la Recherche Scientifique, Universit\u00e9 Toulouse 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