Chen Shixin, Lei Jiangchu, Mou Haochen, Zhang Wenkan, Jin Lingxiao, Lu Senxu, Yinwang Eloy, Xue Yucheng, Shao Zhenxuan, Chen Tao, Wang Fangqian, Zhao Shenzhi, Chai Xupeng, Wang Zenan, Zhang Jiahao, Zhang Zengjie, Ye Zhaoming, Li Binghao
Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China.
Front Immunol. 2024 Feb 23;15:1335366. doi: 10.3389/fimmu.2024.1335366. eCollection 2024.
Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in 'vicious cycle' accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies.
骨是实体瘤转移的常见器官。恶性骨肿瘤在定植后对全身治疗变得不敏感，随后预后不良且复发率高。免疫细胞和骨细胞构成了一个独特的免疫微环境，在骨转移的背景下发挥着关键作用。本综述首先聚焦于骨转移性癌中的淋巴细胞，包括它们在肿瘤播散、侵袭、生长以及可能的细胞毒性诱导清除中的作用。随后，我们研究髓系细胞，即巨噬细胞、髓系来源的抑制细胞、树突状细胞和巨核细胞，评估它们与细胞毒性T淋巴细胞的相互作用以及对骨转移的贡献。作为骨骼组织的重要组成部分，源自骨髓基质细胞的破骨细胞和成骨细胞参与“恶性循环”，加速溶骨性骨转移。我们还解释了肿瘤休眠的概念，并研究免疫微环境对其的潜在作用。此外，本文对临床研究中骨转移性恶性肿瘤的新兴治疗方法，尤其是免疫疗法进行了全面综述，指出了骨转移治疗研发中当前面临的挑战和机遇。
