荷兰伊拉斯谟医学中心癌症研究所Tom Cupedo和Pieter Sonneveld研究组合作取得进展。他们发现在多发性骨髓瘤患者体内，IL-1β诱导的中性粒细胞-间质细胞轴形成富含BAFF的原肿瘤微环境。相关论文于2024年4月10日发表于国际学术期刊《自然-免疫学》杂志上。

研究人员揭示了骨髓瘤相关人类骨髓中性粒细胞的改变，及基质炎症对中性粒细胞功能的影响。骨髓瘤骨髓中的成熟中性粒细胞被激活并支持肿瘤发生，其转录IL1B和骨髓瘤细胞存活因子TNFSF13B（BAFF）的水平升高。与炎性基质细胞的相互作用会诱导中性粒细胞活化，并以STAT3依赖性方式分泌BAFF；中性粒细胞一旦活化就会获得诱导相关基质活化的能力。

髓细胞耗竭性抗一线治疗髓鞘瘤后，人类骨髓中仍具有残余的基质炎症，新形成的中性粒细胞被重新激活。综上所述，该研究揭示了一个中性粒细胞-基质细胞前反馈通路，它导致治疗后仍持续存在的肿瘤支持性炎症，因此有必要研发针对多发性骨髓瘤的基质和免疫微环境进行治疗的新策略。

据介绍，大量中性粒细胞长期存在于人骨髓中，这些细胞对肿瘤的支持偏好性可能会对骨髓封闭恶性肿瘤产生重大影响。在多发性骨髓瘤患者中，骨髓中的炎性基质细胞具有影响中性粒细胞的潜能。

附：英文原文

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

Author: de Jong, Madelon M. E., Fokkema, Cathelijne, Papazian, Natalie, Czeti, gnes, Appelman, Marjolein K., Vermeulen, Michael, van Heusden, Teddie, Hoogenboezem, Remco M., van Beek, Gregory, Tahri, Sabrin, Sanders, Mathijs A., van de Woestijne, Pieter C., Gay, Francesca, Moreau, Philippe, Bttner-Herold, Maike, Bruns, Heiko, van Duin, Mark, Broijl, Annemiek, Sonneveld, Pieter, Cupedo, Tom

Issue&Volume: 2024-04-10

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.

DOI: 10.1038/s41590-024-01808-x

Source: https://www.nature.com/articles/s41590-024-01808-x