Immune regulation of the tumor/bone vicious cycle
Immune regulation of the tumor/bone vicious cycle
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DOI：
10.1111/j.1749-6632.2011.06244.x
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Faccio, Roberta
中科院分区：
文献类型：
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作者：
Faccio, Roberta
骨转移引起的骨破坏是由肿瘤募集的破骨细胞（OCs）介导的。因此，OC是患病个体的主要治疗靶点。另一方面，三分之一的患者在开始抗骨吸收治疗的两年内发生了进一步的骨相关事件，这表明额外的细胞调节了骨肿瘤的生长。先前的研究表明，通过靶向OC改善骨转移是在注射人乳腺癌细胞的免疫受损动物中进行的。因此，免疫系统对骨肿瘤生长的贡献尚不清楚。使用免疫和OC调节的遗传模型（PLC γ 2和林恩），以及OC和T细胞的药理学抑制，我们现在证明，免疫缺陷的条件可以干扰OC阻断的抗肿瘤作用。因此，我们的研究结果扩展了目前的肿瘤/骨恶性循环模型，包括T细胞作为骨肿瘤生长的额外调节因子，无论OC状态如何。
The bone destruction attending skeletal metastasis is mediated by tumor-recruited osteoclasts (OCs). Hence, OCs are principal therapeutic targets in afflicted individuals. On the other hand, one-third of patients develop further skeletal-related events within two years of initiating antiresorptive therapies, suggesting that additional cells modulate bone tumor growth. Previous studies showing amelioration of bone metastases by targeting the OCs were performed in immune-compromised animals injected with human breast cancer cells. Consequently, the contribution of the immune system to bone tumor growth was unclear. Using genetic models of immune and OC modulation (PLC gamma 2 and Lyn), as well as pharmacological inhibition of OCs and T cells, we now demonstrate that a condition of immune deficiency can interfere with the antitumor effects of OC blockade. Thus, our findings expand the current tumor/bone vicious cycle model to include T cells as additional regulators of bone tumor growth, regardless of the OC status.