Macrophage-directed therapeutic strategies in cancer

Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment and exhibit remarkable functional plasticity, acting as either immunosuppressive cells that promote tumor progression or immunostimulatory cells that can support antitumor immunity, depending on the prevailing microenvironmental cues. These cells promote angiogenesis, metastasis, immune suppression, and therapy resistance. However, when appropriately reprogrammed, TAMs can directly kill or phagocytose cancer cells and/or activate antitumor T cell and natural killer cell responses. In this article, we review current therapeutic strategies targeting TAMs, including approaches directed against macrophage-associated receptors, signaling pathways, and epigenetic and metabolic regulators. We also discuss emerging TAM-targeted therapeutic modalities, including cytokine-based therapies, cell-based therapies, bispecific antibodies, macrophage-targeted nanoplatforms, and anti-TAM chimeric antigen receptor T-cell approaches, highlighting their potential to enhance antitumor immunity and improve clinical outcomes.