macrophage

Overview

Macrophages are highly versatile, long-lived phagocytic cells of the innate immune system derived primarily from circulating monocytes and tissue-resident precursors seeded during embryonic development. Found in virtually every tissue of the body, they serve as frontline sentinels that detect, engulf, and destroy pathogens, apoptotic cells, and foreign materials through receptor-mediated phagocytosis and intracellular killing mechanisms. Beyond their classical antimicrobial function, macrophages act as master regulators of inflammation and tissue homeostasis: they secrete a broad array of cytokines and chemokines, present antigens to T lymphocytes, coordinate wound repair, and modulate the activity of adaptive immune cells including regulatory T cells, CD8+ cytotoxic T lymphocytes, dendritic cells, and natural killer (NK) cells.

A defining feature of macrophage biology is their remarkable phenotypic plasticity, operationally categorized into pro-inflammatory (M1-like) and tissue-reparative (M2-like) polarization states, though the true spectrum in vivo is considerably more complex. M1-polarized macrophages are driven by signals such as interferon-γ and bacterial lipopolysaccharide, producing proinflammatory cytokines including Interleukin 1 beta, TNF-α, and NO via inducible nitric oxide synthase (iNOS), while M2-polarized macrophages, induced by IL-4, IL-13, or transforming growth factor-beta, support tissue remodeling, angiogenesis, and immune suppression. This polarization axis has profound clinical relevance: dysregulated macrophage activation drives pathologies ranging from sepsis and autoimmune nephritis to metabolic dysfunction–associated steatotic liver disease and cancer progression, making macrophages one of the most studied cellular targets in translational biomedical research.

Focus of Latest Publications

Recent publications have focused heavily on macrophages as dynamic regulators of inflammation, tissue remodeling, and tumor progression, with particular attention to their plasticity and therapeutic targeting. In cancer, tumor-associated macrophages (TAMs) were described as abundant and heterogeneous cells in the tumor microenvironment that contribute to angiogenesis, metastasis, immune evasion, and therapeutic resistance. A recent review emphasized that single-cell transcriptomics and spatial profiling have moved the field beyond the traditional M1/M2 framework, motivating more refined strategies such as recruitment blockade, depletion of tumor-promoting macrophages, reprogramming, enhancement of phagocytosis and antigen presentation, and biomimetic delivery systems including macrophage membrane coating and macrophage-derived extracellular vesicles.

Several studies explored macrophage-directed nanomedicine and immunotherapy. In cancer, ratio-tunable bispecific nanoparticles combined a sonosensitizer with peptides targeting CD47 and PD-L1; ultrasound activation promoted immunogenic cell death and was reported to enhance dendritic cell maturation, shift macrophages toward an M1-like phenotype, and increase CD8+ T cell infiltration. Another dual-targeting aptamer-drug hybrid delivered doxorubicin and a STING agonist, and the resulting immune remodeling included expansion of IFN-responsive macrophages alongside dendritic cell activation and improved cytotoxic T cell responses. In rheumatoid arthritis, inflammation-targeted nanoaggregates carrying triptolide and hyperoside were designed to selectively target M1 macrophages, promote M1-to-M2 polarization, reduce inflammatory signaling, and reverse oxidative stress while improving joint accumulation and reducing systemic toxicity.

Macrophages were also investigated in nonmalignant inflammatory and regenerative settings. In a mouse endometrial injury model, macrophages rapidly infiltrated the tissue during the early inflammatory phase and were reported to be indispensable for regeneration; they promoted SFRP4+ stromal cell reprogramming through TNF-α, and TNF-α-induced SFRP4+ stromal cells enhanced regeneration after transplantation. In diabetic wound healing, exosome-loaded conductive hydrogels combined with electrical stimulation increased macrophage recruitment and upregulated IL-10 to drive M2 polarization, contributing to reduced inflammation, improved re-epithelialization, collagen deposition, and angiogenesis.

Other publications highlighted macrophage involvement in disease pathology and biomaterial responses. In atherosclerosis, macrophages in plaques were described as influencing inflammation and plaque stability, with iron homeostasis also affecting disease progression; targeted drug delivery to macrophages and the endothelium was presented as a strategy to reduce systemic side effects. In vaccine-induced granulomas, macrophages were shown to contain aluminum-positive vacuoles and crystalloid bodies, and the study provided evidence consistent with in vivo formation of highly ordered γ-Al2O3 microcrystals from γ-AlOOH nanoparticles within macrophages under physiological conditions. Reviews of lung cancer and hydatid cyst components further noted that exosomes and parasite-derived antigens can modulate macrophage polarization and broader immune responses, underscoring the central role of macrophages in immune evasion, immunomodulation, and therapeutic design.

Key Publications

NEWJan TAM-targeted nanomedicine in cancer: biological basis, therapeutic strategies, and translational perspectives. (Theranostics, 2026, PMID 42370186): "With optimization of delivery systems (e.g. particle size, surface chemistry, ligands, therapeutic payloads, and the type of stimuli), multiple functionalities can be engineered to improve macrophage (in the tumor microenvironment) recruitment, depletion, reprogramming, and enhancement of TAM phagocytosis, antigen presentation, and immune regulation."
NEWJun Emerging biomedical and pharmaceutical strategies for the treatment of atherosclerosis: from conventional lipid-lowering therapy to nanomedicine. (Journal of applied biomedicine, 2026, PMID 42333862): "Innovative strategies involve natural products and nanotechnology for targeted drug delivery, especially to macrophages and the endothelium, reducing systemic side effects."
Jun Spatial and temporal single cell multi-omics in mice reveals macrophage-SFRP4+ stroma interactions promoting endometrial regeneration via TNF-α. (Cell reports, 2026, PMID 42234562): "In the early inflammatory stage (0-4 dpi), macrophages rapidly infiltrate and are indispensable for regeneration."
May Macrophage-Mediated In Vivo Intracellular Crystallization of Aluminum Oxyhydroxide Adjuvant in Vaccine-Induced Granulomas. (ACS applied materials & interfaces, 2026, PMID 42062044): "These findings support an in vivo formation of γ-Al2O3 microcrystals from γ-AlOOH nanoparticles within macrophages under physiological conditions."
Apr Ratio-Tunable Dual-Peptide and Ultrasound-Assisted Nanoplatform for Enhancing Personalized Antitumor Immunotherapy. (Advanced materials (Deerfield Beach, Fla.), 2026, PMID 41979280): "ultrasound-activated BiNPs with a selected peptide ratio enhance dendritic cell maturation, shift macrophages toward an M1-like phenotype, increase CD8+ T cell infiltration, and suppress primary and distant tumors with favorable biosafety."
Apr Dual-Targeting Multivalent Aptamer-Drug Hybrids for Synergistic Cancer Immunotherapy. (Journal of the American Chemical Society, 2026, PMID 41973478): "This coordinated action remodels the immunosuppressive tumor microenvironment, promoting dendritic cell recruitment and activation, expanding IFN-responsive macrophages and conventional dendritic cells, and driving the proliferation and functional maintenance of cytotoxic CD8+ T cells."
Mar Inflammation-targeted nanoaggregates encapsulated triptolide and hyperoside for M2 macrophage repolarization and oxidative stress reversal in rheumatoid arthritis therapy. (Colloids and surfaces. B, Biointerfaces, 2026, PMID 41795263): "NPS can selectively target M1 macrophages through HYP's galactose residues, exerting strong anti-inflammatory effects via M1-to-M2 macrophage polarization."
Apr Potential immunomodulatory and antitumor properties of hydatid cysts components. (International immunopharmacology, 2026, PMID 41785598): "activate immune effector cells, including macrophages, natural killer (NK) cells, and T lymphocytes."
Apr Exosome-mediated crosstalk between immune cells and tumor microenvironment in lung cancer: Implications for immune evasion and therapeutic resistance. (Cellular signalling, 2026, PMID 41759799): "Tumor-derived exosomes (TEXs) facilitate immune evasion by impairing cytotoxic T lymphocytes (CTLs) function, promoting regulatory T cells (Tregs) differentiation, and polarizing macrophages toward the tumor-supportive M2 phenotype."
May Multifunctional conductive hydrogel integrating exosome delivery and electrical stimulation for enhanced diabetic wound healing. (Biomaterials advances, 2026, PMID 41576607): "the proliferation, migration, and differentiation of fibroblasts (NIH-3T3), endothelial cells (HUVECs), and macrophages (Raw 264.7) in vitro."