CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression.
Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression.
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多发性骨髓瘤仍然是一种由克隆性扩增的恶性浆细胞引起的 largely 不可治愈的疾病。骨髓微环境中存在治疗耐药的多发性骨髓瘤细胞，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 细胞中高度丰富，为不同的长寿命细胞群体（例如造血干细胞）提供免疫保护龛。
在此，我们探讨了 Tregs 在多发性骨髓瘤向骨髓腔室播散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，我们利用了两种不同遗传背景下的同基因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显示，骨髓 Tregs 积聚在恶性浆细胞附近，并表现出活化表型。体内 Treg 清除在两种模型中均阻止了多发性骨髓瘤播散。
重要的是，在已建立多发性骨髓瘤的小鼠中，短期体内清除 Tregs 引发了强效的 CD8 T 细胞和 NK 细胞介导的免疫反应，导致完全且稳定的缓解。
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。
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.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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