Mechanisms regulating the recruitment of myeloid cells to the tumor microenvironment. (a) Myeloid cells are activated and mobilized from the bone marrow in response to tumor derived factor such as Bv8, SDF-1α, GM-CSF. (b) Circulating myeloid cells express integrin adhesion molecules in an inactive confirmation, with low binding affinity. (c) In response to diverse chemotactic factors released from the tumor microenvironment, myeloid PI3Kγ activates the adhesion molecule integrin α4β1. (d) Myeloid cells are now able to bind to the activated tumor endothelium expressing the integrin α4β1 ligand VCAM-1. (e) Myeloid cells extravasate from the blood stream and migrate toward the tumor microenvironment, (f) where they differentiate in response to the cytokines/chemokine milieu to tumor associated macrophages. Px, Paxillin; Tn, Talin; TAM, tumor associated macrophages.