Macrophage heterogeneity and plasticity: mechanism and therapeutics

Macrophages play pivotal roles in regulating immune responses during inflammation and cancer. Recent evidence indicates that macrophages are dynamic cells capable of switching between different functional states in response to stimuli from their local microenvironment. However, characterizing these functional states in the context of inflammation and cancer has been challenging due to a lack of powerful tools. To address this important issue, recent studies have employed single-cell technologies and emerging immunoinformatics methods to explore the relationship between macrophage phenotypic states and their cellular functions. Here, we synthesize insights from these studies and discuss the current understanding of macrophage diversity (heterogeneity) and adaptability (plasticity) in acute inflammation, chronic diseases, and cancer. We also highlight the molecular mechanisms that initiate macrophage state transitions during disease progression. By integrating knowledge gained from different disease models, we propose a conceptual framework for the future development of pharmacological approaches aimed at targeting macrophages effectively.