Inflamm Res. 2026 Jun 20;75(1):151. doi: 10.1007/s00011-026-02284-9.
ABSTRACT
BACKGROUND: Human oncoviruses infect host cells and drive tumorigenesis. Macrophages, as key innate immune cells, exhibit functional heterogeneity and polarization plasticity. They are broadly classified into proinflammatory M1 and anti-inflammatory M2 states, which determine their role in immunity and tissue homeostasis.
METHODS: We summarized the recent experimental and clinical studies on the interactions between macrophages and the major oncoviruses, including Epstein-Barr virus (EBV), Kaposi’s Sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell leukemia virus type 1 (HTLV-1), and human papillomavirus (HPV). We focus on how viral proteins, non-coding RNAs, and extracellular vesicles reprogram macrophage functions and discuss emerging macrophage-targeted therapeutic strategies.
RESULTS: Oncoviruses drive macrophages toward pro-tumor M2 or dysfunctional M1 states by altering cytokine secretion, activating signaling pathways, such as cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and nuclear factor kappa B (NF-κB), and reprogramming metabolic pathways. New therapeutic strategies targeting macrophages, including polarization modulation, bispecific antibodies, nanomedicine delivery systems, and immune checkpoint strategies, show promise in enhancing antiviral and antitumor immunity.
CONCLUSION: Macrophages can sense various oncoviruses and play a role in oncovirus infection, chronic inflammation, and virus-driven tumorigenesis. Potential therapeutic strategies targeting macrophages offer new avenues for the precision treatment of oncovirus-associated diseases.
PMID:42323450 | DOI:10.1007/s00011-026-02284-9
