CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Identification and validation of ecto-5' nucleotidase as an immunotherapeutic target in multiple myeloma.
Identification and validation of ecto-5' nucleotidase as an immunotherapeutic target in multiple myeloma.
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骨髓（BM）微环境中浆细胞样树突状细胞（pDC）与多发性骨髓瘤（MM）细胞、T 或 NK 效应细胞的相互作用可诱导肿瘤细胞生长，并抑制固有免疫和适应性免疫应答。明确 pDC-MM 相互作用触发的免疫抑制机制，将有助于设计增强抗 MM 免疫的干预性治疗。
在本研究中，我们表明 pDC-MM 相互作用在 pDC 和 MM 细胞中均诱导代谢酶 Ecto-5' Nucleotidase/CD73。MM 患者的基因表达数据库显示，CD73 水平与总生存期呈负相关。利用我们的 pDC-MM 共培养模型，我们发现用抗 CD73 抗体阻断 CD73 可：降低腺苷水平；激活 MM 患者 pDC；触发针对自体患者 MM 细胞的细胞毒性 T 淋巴细胞（CTL）活性。抗 CD73 抗体与免疫刺激剂 TLR-7 激动剂的联合应用可增强自体 MM 特异性 CD8 + CTL 活性。
综上所述，我们的临床前数据表明，单独靶向 CD73 治疗或与 TLR-7 激动剂联合治疗，代表了一种有前景的新型策略，可恢复宿主抗 MM 免疫。
Interaction of plasmacytoid dendritic cells (pDCs) with multiple myeloma (MM) cells, T- or NK-effector cells in the bone marrow (BM) microenvironment induces tumor cell growth, as well as inhibits innate and adaptive immune responses. Defining pDC-MM interaction-triggered immunosuppressive mechanism(s) will enable design of interventional therapies to augment anti-MM immunity. In the present study, we show that pDC-MM interactions induce metabolic enzyme Ecto-5' Nucleotidase/CD73 in both pDCs and MM cells. Gene expression database from MM patients showed that CD73 levels inversely correlate with overall survival.
Using our pDC-MM coculture models, we found that blockade of CD73 with anti-CD73 Abs: decreases adenosine levels; activates MM patient pDCs; triggers cytotoxic T lymphocytes (CTL) activity against autologous patient MM cells. Combination of anti-CD73 Abs and an immune-stimulating agent TLR-7 agonist enhances autologous MM-specific CD8 + CTL activity. Taken together, our preclinical data suggest that the therapeutic targeting of CD73, alone or in combination with TLR-7 agonist, represents a promising novel strategy to restore host anti-MM immunity.
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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