Immune regulation of bone metastasis.
Immune regulation of bone metastasis.
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DOI：
10.1038/bonekey.2014.95
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发表时间：
2014-01-01
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：
Capietto, Aude-Helene;Faccio, Roberta
约70%的转移性前列腺癌和乳腺癌患者发生骨转移。不幸的是，骨转移导致显著的发病率和死亡率，并且治疗选择有限。因此，大量的努力集中在了解驱动肿瘤扩散到骨的机制上。骨转移的典型特征在于自我延续的“恶性”循环，其中肿瘤细胞和骨吸收细胞（破骨细胞）被锁定在导致破骨细胞驱动的骨破坏和骨储存因子的释放的循环中，所述骨储存因子继而刺激肿瘤细胞增殖和存活。为了打破这种“恶性”循环，已经使用了有效的抗吸收剂，如唑来膦酸（ZOL）。然而，在临床环境中，ZOL未能改善癌症患者的总生存率，即使它抑制破骨细胞的再吸收活性。因此，除破骨细胞外的其他细胞可能参与调节骨中的肿瘤生长。免疫系统具有消除肿瘤细胞的能力。然而，肿瘤细胞可以获得逃避免疫控制的能力。我们最近的观察表明，免疫细胞识别和杀死肿瘤的能力下降，甚至当破骨细胞被有效的抗吸收剂抑制时，也会导致肿瘤向骨的扩散。本文综述了骨转移过程中涉及的各种免疫细胞群的抗肿瘤和促肿瘤作用。我们还讨论了增强抗肿瘤免疫应答和绕过癌症免疫耐药性的策略。
Metastases to bone occur in about 70% of patients with metastatic prostate and breast cancers. Unfortunately, bone metastases result in significant morbidity and mortality and treatment options are limited. Thus, significant effort has focused on understanding the mechanisms that drive tumor dissemination to bone. Bone metastases are typically characterized by a self-perpetuating 'vicious' cycle wherein tumor cells and bone-resorbing cells (osteoclasts) are locked in a cycle that leads to osteoclast-driven bone destruction and the release of bone-stored factors that in turn stimulate tumor cell proliferation and survival. To break this 'vicious' cycle, potent antiresorptive agents such as zoledronic acid (ZOL) have been used. However, in the clinical setting, ZOL failed to improve the overall survival of cancer patients even though it inhibited osteoclast resorptive activity. Thus, other cells in addition to osteoclasts are likely involved in modulating tumor growth in the bone. The immune system has the ability to eliminate tumor cells. Nevertheless, tumor cells can acquire the ability to escape immune control. Our recent observations indicated that a decline in the ability of the immune cells to recognize and kill the tumor drives tumor dissemination to bone even when osteoclasts are inhibited by potent antiresorptive agents. This review focuses on the antitumor and protumor effects of various immune cell populations involved in the bone metastatic process. We also discuss strategies to enhance antitumor immune responses and bypass cancer immune resistance.