Macrophages, Neutrophils, and Cancer: A Double Edged Sword

The tumor microenvironment is a well-recognized framework, in which myeloid cells play important roles in cancer development from tumor initiation to metastasis. Immune cells present in the tumor microenvironment can promote or inhibit cancer formation and development. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to distinct signals the cells of the monocyte-macrophage lineage have the ability to display a wide spectrum of activation states; classical Ml or alternative M2 macrophages represent extremes of a continuum of this activation. Tumor-associated macrophages generally acquire an M2-like phenotype that is relevant for their participation in tumor growth and progression. There is now evidence that also neutrophils can be driven towards distinct phenotypes in response to microenvironmental signals. In fact they can interact with distinct cell populations and produce a wide number of cytokines and effector molecules. Therefore, macrophages and neutrophils are both integrated in the regulation of the innate and adaptive immune responses in various inflammatory situations, including cancer. These findings have triggered efforts to target tumor-associated macrophages and neutrophils. In particular, “reeducation” to activate their antitumor potential or elimination of tumor promoting cells is a new strategy undergoing preclinical and clinical evaluation.