Fig. 3
From: Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?
Interactions between CTCs and immune cells. CTC interaction with immune cells in the circulation is central to both their survival and ability to form metastatic niches. a NK cells, b T-cells, c macrophages, and d neutrophils in the blood circulation have all be found to interact with CTCs. CTCs have shown the ability to resist TRAIL-induced apoptosis via autophagic removal of death receptor 5 (DR5) in vitro, thus circumventing cytokine-mediated immune surveillance. CTCs also have been found to express PD-L1 receptor and interact with T-cell PD-1 to reduce anti-CTC T-cell function. Expression of CTC PD-L1 may prevent T-cell mediated cell destruction and offer a potential therapeutic target towards CTCs. Expression of CD47 on CTCs may stimulate “don’t eat me” signals, evading macrophage-mediated phagocytosis and promoting intercellular adhesion and migration of CTCs. Neutrophils, using both direct cell contact and through the production of extracellular traps can promote the metastatic potential of CTCs through increased cellular proliferation. VCAM-1 and β-Integrin1 interactions between CTCs and neutrophils promotes an inflammatory milieu that is conducive for CTC extravasation and formation of the metastatic niche. CTCs too use CCDC25 to sense neutrophil extracellular DNA produced by NETs deposits in organs acting as a chemotactic factor to attract CTCs for distal metastasis