Abstract
Macrophages are one of the most abundant immune cells in the tumour microenvironment of solid tumours and their presence correlates with reduced survival in most cancers. Macrophages are present at all stages of tumour progression and stimulate angiogenesis, tumour cell invasion, and intravasation at the primary site. At the metastatic site, macrophages and monocytes prepare for the arrival of disseminated tumour cells and promote their extravasation and survival by inhibiting immune-mediated clearance or by directly engaging with tumour cells to activate prosurvival signalling pathways. In addition, macrophages promote the growth of disseminated tumour cells at the metastatic site by organising the formation of a supportive metastatic niche. The development of agents inhibiting the recruitment or the protumorigenic effector functions of macrophages in both the primary tumour and at the metastatic site is a promising strategy to improve cancer survival in the future.
Highlights
Macrophages and monocytes prepare for the arrival of disseminated tumour cells and promote their extravasation and survival by inhibiting immune-mediated clearance or by directly engaging with tumour cells to activate prosurvival signalling pathways
Tissue-resident macrophages can develop from three independent sources during embryonic development and adulthood: yolk sac-derived macrophages and fetal liverderived monocytes or hematopoietic stem cells in the bone marrow
Fate mapping has identified yolk sac-derived macrophages as the main precursor for brain microglia [11], whereas fetal liverderived monocytes are the main precursor of liver Kupffer cells and lung alveolar macrophages [12, 13], while bone marrow-derived monocytes replenish intestinal and cardiac macrophages in the steady state adult organism [14, 15]
Summary
Monocytes and macrophages are a subset of leukocytes that play distinct roles in tissue homeostasis and immunity. Tissue-resident macrophages are capable of maintaining their populations through proliferation, which means that in the adult steady state organism, monocytes do not contribute to the maintenance of most peripheral tissue macrophages This includes microglia in the brain, Kupffer cells in the liver, and Langerhans cells in the epidermis [7,8,9,10]. Using flow cytometry and different genetic mouse models, it was recently demonstrated in breast cancer that tumour growth was associated with a decrease in mammary tissue macrophages and an increase in tumour-associated macrophages (TAMs) These TAMs were distinguished from mammary-resident macrophages based on the surface expression of CD11blow MHCIIhigh F4/80+ CD64+ MerTK+ on TAMs. These TAMs were distinguished from mammary-resident macrophages based on the surface expression of CD11blow MHCIIhigh F4/80+ CD64+ MerTK+ on TAMs This TAM population was recruited directly from CCR2+ inflammatory monocytes that proliferated and differentiated into TAMs in the tumour microenvironment [31].
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