Macrophages and cancer: from mechanisms to therapeutic implications

• Circulating monocytes are the primary source of TAMs in many tumors.
• TAM properties are shaped by tissue- and tumor-specific microenvironmental signals.
• The ensuing TAM heterogeneity is not captured by the classical M1/M2 nomenclature.
• TAM depletion or reconditioning has therapeutic relevance in specific tumors.

Infiltration by immune cells is a hallmark of most forms of malignancy. In this context, tumor-associated macrophages (TAMs) represent key regulators of the complex interplay between the immune system and cancer. We discuss evidence indicating that in many settings TAMs fuel, rather than limit, tumor progression, and negatively impact on responses to therapy. We discuss how the unique functional properties of TAMs are shaped by tumor-derived signals, placing TAM development in the context of the broader understanding of the cellular and molecular mechanisms controlling macrophage origin, differentiation, and maintenance in tissues. Finally, we provide examples of how a molecular understanding of the relationships between TAMs and the tumor microenvironment may lead to improved cancer therapies.