Macrophages: Key orchestrators of a tumor microenvironment defined by therapeutic resistance

Macrophages have emerged as promising therapeutic targets in cancer. Within tumor tissue, macrophages foster tumor development, invasion, and metastasis. As the phenotype of macrophages is inherently pliable and dependent on cues received from the surrounding microenvironment, macrophages co-evolve with malignant and other non-malignant cells during cancer progression. In doing so, they establish a microenvironment that is therapeutically resistant and thwarts the productivity of T cell immunosuveillance. Strategies designed to deplete, inhibit, or redirect macrophages with anti-tumor activity are being explored to reverse the pro-tumor properties of macrophages that are commonly observed in cancer. In this review, we discuss our current understanding of the mechanisms that regulate macrophage recruitment to tumors, their impact on the tumor microenvironment, and their promise as therapeutic targets for improving the efficacy of cytotoxic- and immune-based therapies.