The Contribution of the Immune System in Bone Metastasis Pathogenesis

Abstract

Bone metastasis is associated with significant morbidity for cancer patients and results in a reduced quality of life. The bone marrow is a fertile soil containing a complex composition of immune cells that may actually provide an immune-privileged niche for disseminated tumor cells to colonize and proliferate. In this unique immune milieu, multiple immune cells including T cells, natural killer cells, macrophages, dendritic cells, myeloid-derived suppressor cells, and neutrophils are involved in the process of bone metastasis. In this review, we will discuss the crosstalk between immune cells in bone microenvironment and their involvement with cancer cell metastasis to the bone. Furthermore, we will highlight the anti-tumoral and pro-tumoral function of each immune cell type that contributes to bone metastasis. We will end with a discussion of current therapeutic strategies aimed at sensitizing immune cells.

Oestrogen and zoledronic acid driven changes to the bone and immune environments: Potential mechanisms underlying the differential anti-tumour effects of zoledronic acid in pre- and post-menopausal conditions

“…Depending on the cytokines acting on the precursors, macrophages can differentiate into two broad classes. Firstly, pro-inflammatory anti-tumour macrophages, secreting IL-1, IL-6, IL-12 and IFN-γ to recruit T cells and eliminate tumour cells [81] . Secondly, tumour associated macrophages (TAMs) which are considered one of the most important regulators of tumour progression and bone metastasis [82] since they secrete cytokines such as IL-10 and TGF-β which decrease CD4 + and CD8 + T cell activity on the tumour microenvironment [83] .…”

Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization

“…As a unit, the bone and bone marrow show a tight functional correlation [ 24 ]. Cancer cells cause destruction of bone, and cytokines secreted by bone marrow cells may also take part in cancer progression, during which, crosstalk is established between bone and cancer [ 42 ]. Bone marrow compartment is composed of multiple cells, such as hematopoietic stem/progenitor cells, mesenchymal stem cells, immune cells, osteoclasts and osteoblasts [ 43 ], and is a favorable metastatic site for cancer cells [ 44 , 45 ].…”

Immunotherapies and Metastatic Cancers: Understanding Utility and Predictivity of Human Immune Cell Engrafted Mice in Preclinical Drug Development

“…Immunotherapies are currently studied in different metastatic cancers as mono-and combination therapies [52]. Targeting of immune cells in metastasis can be TME-dependent and many highly immunosuppressive sites, such as bone marrow, may be less responsive to immunotherapies [53,54]. Although metastases have been vastly studied in general, studying immune cells and immunotherapies has been less intensive, especially in preclinical animal models, despite one of the earliest studies dating back to the 1970's [55].…”