Tumor promotes the recruitment of myeloid- and mesenchymal-derived suppressor cells. Tumor formation is associated with the recruitment of cells of myeloid and mesenchymal origin that, as a consequence of the tumor secretome, are polarized toward an antiinflammatory and immunosuppressive profile. Circulating fibrocytes detected in patients with metastatic tumor display features of the myeloid compartment and exert immunosuppressive activity in vitro. Because of these characteristics, fibrocytes can be affiliated to the group of MDSCs. The immunosuppressive activity can be attributed to the production of IDO, which depletes the cellular microenvironment of tryptophan, required for T-cell proliferation. Despite substantial differences in marker expression and lineage of origin, IDO is also the main mechanism by which tumor-polarized DCs or MSCs inhibit immune responses. In contrast, polarized monocytes, macrophages, and neutrophils preferentially use a different set of molecules including arginase, nitric oxide, interleukin (IL)-4, IL-10, and IL-13.