Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors

Abstract

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 in situ 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.

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner

“…Although the intracardiac injection method is widely used for assessing experimental metastatic colonization of cancer cells, the overall metastatic burden in this in vivo assay is also influenced by tumor cell survival in the circulation as well as extravasation ability of tumor cells at the metastatic site. Furthermore, while in vivo studies involving human cancer cells necessitate the use of immunodeficient animals, since immune cells have a multitude of effects on OBs and OCLs in bone metastatic microenvironment thereby dictating the outgrowth behavior of cancer cells (43), fully immunocompetent mouse models are more physiologically relevant model systems. Therefore, in our next set of experiments, we performed direct intratibial injection of control vs MRTF-knockdown D2A1 cells in syngeneic immunocompetent Balb/c mice.…”