摘 要：鼻咽癌是东南亚及中国南方高发的恶性肿瘤，与EB病毒感染密切相关。尽管早期放化疗局部控制较好，但其复发、转移及耐药仍是主要挑战。免疫细胞在肿瘤进展中起关键作用，其中巨噬细胞起源于骨髓造血干细胞（经单核细胞分化），作为固有免疫核心成员广泛分布于组织，参与炎症调控、组织修复等生理过程。肿瘤相关巨噬细胞（TAMs）是肿瘤微环境的核心成分，由肿瘤分泌的细胞因子招募单核细胞分化形成，具有高度的可塑性，可分为促癌的M2型与抑癌的M1型。M2型TAMs通过促进肿瘤的增殖、侵袭、血管生成及免疫抑制［如高表达程序性死亡配体1（PD-L1）、分泌白细胞介素-10（IL-10）］驱动进展；M1型则通过抗体依赖性细胞介导的细胞毒性（ADCC）作用、活性氧/一氧化氮（ROS/NO）诱导凋亡，直接杀伤肿瘤，并通过增强抗原提呈和促进CD8⁺ T细胞浸润来激活适应性免疫。临床研究显示，M2型TAMs高浸润与患者生存率降低、放化疗耐药及免疫治疗应答率下降相关，是潜在的预后标志物和治疗靶点。当前针对TAMs的治疗策略包括阻断CCL2-CCR2/CSF-1R信号轴以抑制M2招募、通过表观调控或CD40双特异性抗体增强M1功能、利用氯膦酸盐脂质体或光热/光动力清除促癌TAMs以及联合放化疗或免疫治疗等。本文系统综述了TAMs在鼻咽癌中的起源、分型、功能及临床关联，总结了其靶向治疗策略进展，为鼻咽癌个体化治疗提供了理论与实践参考。

关键词：鼻咽癌；肿瘤相关巨噬细胞；肿瘤微环境；巨噬细胞极化；靶向治疗
中图分类号：R739.62      文献标志码：A                   DOI：10.3969/j.issn.1007-7146.2025.06.004

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）