{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:42:21Z","timestamp":1792798941635,"version":"4.5.0"},"reference-count":49,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,13]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Understanding the roles of myeloid cells in the tumor microenvironment (TME) has emerged as a promising strategy to identify novel targets to counteract the immunosuppressive barriers protecting multiple myeloma (MM). Neutrophils are a new cancer research focus due to their potential to reduce the efficacy of immune-based therapies. This study aimed to deepen understanding of neutrophil function in MM by analyzing freshly isolated myeloid cells from paired focal lesions (FLs) and bone marrow using single-cell RNA sequencing, immunofluorescence imaging, and functional assays. We describe 3 distinct CXCR2+ mature neutrophil subsets: TREM1+CD10+, RETN+LCN2+, and TNFAIP3+CXCL8+, each exhibiting unique phenotypes within the TME. Notably, the TREM1+CD10+ subset was highly prevalent, particularly in FLs, demonstrating potent immunosuppressive effects on T cells. This subset\u2019s gene signature was correlated with shorter overall survival (OS) in a large data set of patients with MM, underscoring its clinical significance. Targeted inhibition of neutrophil activity through CXCR2 blockade, alone or combined with standard anti-MM therapies, significantly reduced tumor burden, improving OS in preclinical MM models. These insights into neutrophil-mediated immunosuppression in MM provide valuable knowledge regarding mechanisms driving immune evasion, and reveal new therapeutic approaches to enhance the efficacy of MM treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025028963","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T20:01:46Z","timestamp":1754337706000},"page":"2392-2405","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Deciphering neutrophil dynamics in the focal lesion tumor microenvironment to overcome immunosuppression in multiple myeloma"],"prefix":"10.1182","volume":"146","author":[{"given":"Joshua","family":"Rivera","sequence":"first","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 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