Abstract: Nasopharyngeal carcinoma (NPC) is a highly prevalent malignant tumor in Southeast Asia and Southern China, with a strong association with Epstein-Barr virus (EBV) infection. Although early-stage NPC exhibits favorable local control with chemoradiotherapy, recurrence, metastasis, and drug resistance remain major clinical challenges. Immune cells play a critical role in tumor progression, among which macrophages — originating from bone marrow hematopoietic stem cells (differentiated via monocytes) — serve as core components of innate immunity, widely distributed in tissues to regulate inflammation and tissue repair. Tumor-associated macrophages (TAMs), a central constituent of the tumor microenvironment, are recruited and differentiated from monocytes by tumor-secreted cytokines, displaying high plasticity with two primary subtypes: pro-tumor M2 and anti-tumor M1. M2-type TAMs drive tumor progression by promoting proliferation, invasion, angiogenesis, and immunosuppression, e. g. , overexpressing programmed death-ligand 1 (PD-L1) and secreting interleukin-10 (IL-10). In contrast, M1-type TAMs exert direct anti-tumor effects through antibody-dependent cellular cytotoxicity (ADCC), reactive oxygen species/nitric oxide (ROS/NO)-induced apoptosis, and activation of adaptive immunity via enhanced antigen presentation and CD8+ T-cell infiltration. Clinical studies indicate that high infiltration of M2-type TAMs correlates with reduced patient survival, chemoradiotherapy resistance, and diminished immunotherapy response, highlighting their potential as prognostic biomarkers and therapeutic targets. Current therapeutic strategies targeting TAMs include: inhibiting M2 recruitment by blocking the CCL2-CCR2/CSF-1R signaling axis; enhancing M1 function via epigenetic regulation or CD40 bispecific antibodies; depleting pro-tumor TAMs using clodronate liposomes or photothermal/photodynamic therapy; and combining with chemoradiotherapy or immunotherapy. This article systematically reviews the origin, classification, functions, and clinical relevance of TAMs in NPC, summarizes advancements in targeted therapeutic strategies, and provides theoretical and practical insights for individualized NPC treatment.
Key words: nasopharyngeal carcinoma; tumor-associated macrophages; tumor microenvironment; macrophage polarization; targeted therapy
（Acta Laser Biology Sinica, 2025, 34(6): 504-514）