Roles of the RANKL-RANK Axis in Immunity-Implications for Pathogenesis and Treatment of Bone Metastasis.
Roles of the RANKL-RANK Axis in Immunity-Implications for Pathogenesis and Treatment of Bone Metastasis.
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RANKL - RANK 轴在免疫中的作用 - 对骨转移发病机制和治疗的影响
DOI：
10.3389/fimmu.2022.824117
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发表时间：
2022
影响因子：
7.3
通讯作者：
Zhou P
中科院分区：
文献类型：
--
作者：
Li B;Wang P;Jiao J;Wei H;Xu W;Zhou P
大量癌症患者会发生骨转移，其中70%的转移性前列腺癌和乳腺癌患者存在骨转移。尽管晚期癌症的全身治疗取得了进展，但骨转移患者的生存率仍然很差。骨细胞和免疫系统之间的相互作用有助于更好地了解免疫系统在癌症骨转移中所起的作用。免疫和骨系统共享各种分子，包括转录因子、信号分子和膜受体，这些分子可以刺激骨吸收破骨细胞的分化和激活。癌症骨转移过程会导致骨转换失调，导致骨质流失和骨骼相关事件 (SRE)，该过程也受到调节肿瘤内微环境和细胞免疫过程的主要癌症相关因素的控制。核因子 kappa B 配体 (RANKL) 和核因子 kappa B 受体激活剂 (RANK) 是破骨细胞发育、骨代谢、淋巴结发育和 T 细胞/树突状细胞通讯的关键调节因子。 RANKL 是一种连接骨骼和免疫系统的破骨细胞因子。在这篇综述中，我们重点介绍了RANKL和RANK在免疫微环境和骨转移中的作用，并回顾了免疫调节机制在骨转移中的作用的数据，这可以通过RANKL抑制剂对骨转移癌症患者的临床疗效来验证。随着RANK信号在破骨细胞生成中的特定作用的发现，针对RANKL的人源化单克隆抗体（例如地诺塞麦）可用于预防骨质流失、SRE和骨转移，为靶向RANKL/RANK作为预防骨转移的未来策略提供了独特的机会。
A substantial amount patients with cancer will develop bone metastases, with 70% of metastatic prostate and breast cancer patients harboring bone metastasis. Despite advancements in systemic therapies for advanced cancer, survival remains poor for those with bone metastases. The interaction between bone cells and the immune system contributes to a better understanding of the role that the immune system plays in the bone metastasis of cancer. The immune and bone systems share various molecules, including transcription factors, signaling molecules, and membrane receptors, which can stimulate the differentiation and activation of bone‐resorbing osteoclasts. The process of cancer metastasis to bone, which deregulates bone turnover and results in bone loss and skeletal-related events (SREs), is also controlled by primary cancer-related factors that modulate the intratumoral microenvironment as well as cellular immune process. The nuclear factor kappa B ligand (RANKL) and the receptor activator of nuclear factor kappa B (RANK) are key regulators of osteoclast development, bone metabolism, lymph node development, and T-cell/dendritic cell communication. RANKL is an osteoclastogenic cytokine that links the bone and the immune system. In this review, we highlight the role of RANKL and RANK in the immune microenvironment and bone metastases and review data on the role of the regulatory mechanism of immunity in bone metastases, which could be verified through clinical efficacy of RANKL inhibitors for cancer patients with bone metastases. With the discovery of the specific role of RANK signaling in osteoclastogenesis, the humanized monoclonal antibody against RANKL, such as denosumab, was available to prevent bone loss, SREs, and bone metastases, providing a unique opportunity to target RANKL/RANK as a future strategy to prevent bone metastases.
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DOI：
10.1083/jcb.142.5.1347
发表时间：
1998-09-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Adebanjo OA;Moonga BS;Yamate T;Sun L;Minkin C;Abe E;Zaidi M
通讯作者：
Zaidi M
影响因子：
11.5
作者：
Ahern, Elizabeth;Harjunpaa, Heidi;Smyth, Mark J.
通讯作者：
Smyth, Mark J.
影响因子：
4
作者：
Bhattacharyya, RS;Stern, PH
通讯作者：
Stern, PH
影响因子：
64.8
作者：
Ansel, KM;Ngo, VN;Cyster, JG
通讯作者：
Cyster, JG
影响因子：
64.8
作者：
Anderson, DM;Maraskovsky, E;Galibert, L
通讯作者：
Galibert, L