An IL-1β-driven neutrophil-stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma.

Autor: de Jong MME; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Fokkema C; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Papazian N; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Czeti Á; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.; Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary., Appelman MK; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Vermeulen M; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., van Heusden T; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Hoogenboezem RM; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., van Beek G; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Tahri S; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Sanders MA; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., van de Woestijne PC; Department of Cardiothoracic Surgery, Erasmus Medical Center, Rotterdam, the Netherlands., Gay F; Clinical Trial Unit, Division of Hematology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy., Moreau P; Department of Hematology, Nantes University Hospital Hotel-Dieu, Nantes, France., Büttner-Herold M; Department of Internal Medicine 5, Hematology and Oncology, Friedrich Alexander University Erlangen-Nuremberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany., Bruns H; Department of Internal Medicine 5, Hematology and Oncology, Friedrich Alexander University Erlangen-Nuremberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany., van Duin M; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Broijl A; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands., Sonneveld P; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands. p.sonneveld@erasmusmc.nl., Cupedo T; Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands. t.cupedo@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 May; Vol. 25 (5), pp. 820-833. Date of Electronic Publication: 2024 Apr 10.
DOI: 10.1038/s41590-024-01808-x
Abstrakt: Human bone marrow permanently harbors high numbers of neutrophils, and a tumor-supportive bias of these cells could significantly impact bone marrow-confined malignancies. In individuals with multiple myeloma, the bone marrow is characterized by inflammatory stromal cells with the potential to influence neutrophils. We investigated myeloma-associated alterations in human marrow neutrophils and the impact of stromal inflammation on neutrophil function. Mature neutrophils in myeloma marrow are activated and tumor supportive and transcribe increased levels of IL1B and myeloma cell survival factor TNFSF13B (BAFF). Interactions with inflammatory stromal cells induce neutrophil activation, including BAFF secretion, in a STAT3-dependent manner, and once activated, neutrophils gain the ability to reciprocally induce stromal activation. After first-line myeloid-depleting antimyeloma treatment, human bone marrow retains residual stromal inflammation, and newly formed neutrophils are reactivated. Combined, we identify a neutrophil-stromal cell feed-forward loop driving tumor-supportive inflammation that persists after treatment and warrants novel strategies to target both stromal and immune microenvironments in multiple myeloma.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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