The Yin‐Yang of tumor‐associated macrophages in neoplastic progression and immune surveillance

Summary: An intrinsic (oncogene‐driven) pathway and an extrinsic (microenvironment‐driven) pathway connect inflammatory reactions and cancer. M2‐polarized tumor‐associated macrophages and the related myeloid‐derived suppressor cells are key prototypic components of smoldering inflammation driving neoplastic progression. However, mononuclear phagocytes can exert anti‐tumor activity by killing tumor cells and eliciting tissue disruptive reactions (M1), a likely scenario in the early phases of carcinogenesis of immunogenic tumors and following therapeutic intervention. Shifting the macrophage balance represents a viable therapeutic target. Herein, the ‘macrophage balance’ is discussed in the context of the apparent paradox of tumor promotion by innate immunity‐driven inflammation and the seemingly opposed tumor surveillance by adaptive immune responses.