CTCs release soluble mediators, such as adenosine diphosphate (ADP), thromboxane (TX) A2, or high-mobility group box 1 (HMGB1), that can ligate toll-like receptor 4 (TLR4) to instigate localized platelet activation and form thrombus encasing tumor cells, thus protecting them from cytolysis by NK cells (Aitokallio-Tallberg et al., 1985; Nieswandt et al., 1999; Yu et al., 2014; Zucchella et al., 1989). Here, HMGB1 is linked to neoplasm.