Abstract

Macrophages are highly plastic and versatile immune cells that play crucial roles in tissue homeostasis, immune surveillance, and inflammation. In both cancer and autoimmune disorders, macrophages adopt altered phenotypes that contribute to disease progression. In tumors, macrophages often differentiate into tumor-associated macrophages (TAMs), which support tumor growth, suppress anti-tumor immunity, and promote metastasis. Conversely, in autoimmune diseases, dysregulated macrophage activity and sustained pro-inflammatory responses exacerbate tissue damage and chronic inflammation. This review explores the dual role of macrophages in cancer and autoimmune diseases, highlighting the mechanisms by which they influence disease outcomes. It further discusses emerging therapeutic strategies aimed at modulating macrophage activity, including reprogramming of macrophage polarization (M1 vs. M2), inhibition of macrophage recruitment, and utilization of monoclonal antibodies and small molecules to target key signaling pathways. The therapeutic targeting of macrophages represents a promising and rapidly evolving frontier in the treatment of both oncologic and autoimmune pathologies, offering new hope for precision medicine and immune-based therapies.