An IL-1β-driven neutrophil–stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma
de Jong MM, Fokkema C, Papazian N, Czeti Á, Appelman MK, Vermeulen M, van Heusden T, Hoogenboezem RM, van Beek G, Tahri S, Sanders MA, van de Woestijne PC, Gay F, Moreau P, Büttner-Herold M, Bruns H, van Duin M, Broijl A, Sonneveld P, Cupedo T (2024)
Publication Type: Journal article
Publication year: 2024
Journal
DOI: 10.1038/s41590-024-01808-x
Abstract
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.
Authors with CRIS profile
Maike Büttner-Herold
Medizinische Fakultät
Heiko Bruns
Department of Medicine 5 – Haematology and Oncology
Involved external institutions
Erasmus University Medical Center (MC)
Netherlands (NL)
Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Italy (IT)
Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU)
France (FR)
Netherlands (NL)
Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Italy (IT)
Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU)
France (FR)
How to cite
APA:
de Jong, M.M., Fokkema, C., Papazian, N., Czeti, Á., Appelman, M.K., Vermeulen, M.,... Cupedo, T. (2024). An IL-1β-driven neutrophil–stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma. Nature Immunology. https://doi.org/10.1038/s41590-024-01808-x
MLA:
de Jong, Madelon M.E., et al. "An IL-1β-driven neutrophil–stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma." Nature Immunology (2024).
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