Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response

Bone is a frequent site of metastasis from several organs and a host for cancer cells that have originated from the bone marrow itself. Skeletal malignancies are extremely difficult to treat. This is largely due to the complex, heterogenous nature of the bone marrow microenvironment and the dynamic interplay between the tumor cells and multiple cell types within the marrow niche. One cell type whose dominant role in supporting tumor progression and therapy evasion is being increasingly recognized are bone marrow adipocytes (BMAs). BMAs are metabolically active endocrine cells that supply lipids, hormones and adipocytokines to the neighboring cells. Their numbers in bone marrow increase with age, obesity and in response to certain treatments and metabolic conditions. BMAs have been shown to directly promote tumor growth through a transfer of lipids, upregulation of lipid transporters, modulation of tumor metabolism and activation of adaptive stress mechanisms in the cancer cells to promote survival. Less is known, however, regarding how adipocyte interactions with other cell types in the bone tumor microenvironment support malignant progression. This review summarizes recent findings on the crosstalk between BMAs and immune cells in bone. We focus specifically on how adipocyte-mediated changes in the immune milieu impact the tumor cell survival and therapy response. We also discuss how adipocyte-immune cell interactions alter bone homeostasis to support malignant progression in a context of current therapeutic strategies for skeletal malignancies.