Figure 2.

Mechanisms underlying the recruitment of monocytes/macrophages into tumors. Circulating monocytes and tissue-resident macrophages are mobilized into the tumor in response to multiple microenvironmental cues such as cytokines, chemokines, ECM components, and hypoxia. Hypoxic areas release higher amount of chemoattractants such as EMAPII, endothelin, and VEGF-A that enhance macrophage migration to these hypoxic sites. Hypoxia also restrains macrophages by decreasing their mobility through the upregulation of MKP-1 enzymes; this terminates the macrophage response to chemoattractants outside the hypoxic areas.