Macrophage Plasticity: Phenotypic and Functional Profiles Across Pathological Microenvironments

Area of Science:

• Immunology
• Cell Biology
• Pathology

Background:

• Macrophages are innate immune cells with high plasticity.
• They adopt context-dependent phenotypes influenced by origin and microenvironment, moving beyond discrete M1/M2 states.
• This plasticity is crucial in various diseases.

Purpose of the Study:

• To review molecular mechanisms shaping macrophage identity.
• To explore macrophage plasticity across a spectrum of diseases.
• To discuss emerging biomarkers and therapeutic strategies.

Main Methods:

• Review of molecular circuits including TLR/cytokine signaling, microRNA networks, metabolic rewiring, and epigenetic mechanisms like histone lactylation.
• Analysis of monocyte subset contributions to tissue macrophage diversity.
• Examination of high-dimensional flow cytometry and mass cytometry (CyTOF) for integrated phenotyping.

Main Results:

• Macrophage pathogenic phenotypes are context-dependent (e.g., M2-like TAMs in cancer vs. M1 in autoimmunity).
• Soluble markers (sCD163, sCD14, soluble mannose receptor) show potential as disease biomarkers.
• Advanced cytometry techniques enable comprehensive analysis of macrophage states.

Conclusions:

• Macrophage plasticity is a central theme in disease pathogenesis and progression.
• Targeting macrophage phenotypes offers promising therapeutic avenues, including TAM reprogramming and CAR-M cells.
• Future research should focus on spatially resolved multi-omics, epigenetic/metabolic targeting, and standardized cytometry for personalized interventions.