Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4⁺FoxP3⁺ regulatory T cells (Tregs) are highly abundant amongst CD4⁺ T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.

多发性骨髓瘤仍然是一种很大程度上无法治愈的克隆性增殖恶性浆细胞疾病。骨髓微环境含有耐药性骨髓瘤细胞，最终导致患者疾病复发。在骨髓中，CD4 ⁺ FoxP3 ⁺调节性 T 细胞 (Tregs) 在 CD4 ⁺T 细胞为不同的长寿命细胞群（例如造血干细胞）提供免疫保护生态位。在这里，我们讨论了 Tregs 在多发性骨髓瘤传播到骨髓隔室和疾病进展中的功能作用。为了研究多发性骨髓瘤的免疫调节，我们在两种不同的遗传背景中使用了同系免疫活性小鼠多发性骨髓瘤模型。分析多发性骨髓瘤的空间免疫结构表明，骨髓 Tregs 聚集在恶性浆细胞附近并显示出激活的表型。体内 Treg 耗竭阻止了两种模型中的多发性骨髓瘤传播。重要的，在患有多发性骨髓瘤的小鼠体内短期内消耗 Tregs 会引起有效的 CD8 T 细胞和 NK 细胞介导的免疫反应，从而导致完全和稳定的缓解。总之，这项临床前体内研究表明，Tregs 是治疗多发性骨髓瘤的一个有吸引力的靶点。