One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage
lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells
are educated by the tumor milieu, rich in cancer cells and stroma components, to exert
functions such as promotion of tumor growth, immunosuppression, angiogenesis, and
cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated
macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental
molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12,
IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals. We discuss
how these factors converge on intracellular determinants (STAT3, STAT6, STAT1, NF-κB,
RORC1, and HIF-1α) of cell functions and drive the recruitment
and polarization of TAMs. Since microRNAs (miRNAs) modulate macrophage polarization
key miRNAs (miR-146a, miR-155, miR-125a, miR-511, and miR-223) are also discussed
in the context of the inflammatory myeloid tumor compartment. Accumulating evidence
suggests that high TAM infiltration correlates with disease progression and overall
poor survival of cancer patients. Identification of molecular targets to develop new
therapeutic interventions targeting these harmful tumor infiltrating myeloid cells
is emerging nowadays.
