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肿瘤相关巨噬细胞在食管鳞癌中的作用机制及靶向治疗前景

Tumor-Associated Macrophages in Esophageal Squamous Cell Carcinoma: Underlying Mechanisms and Targeted Therapy Perspectives

  • 摘要: 肿瘤相关巨噬细胞(TAMs)是塑造食管鳞癌免疫抑制性微环境、驱动其恶性进展的关键免疫群体。本文综述了TAMs通过促进肿瘤增殖、血管生成、转移及治疗抵抗等多种途径参与食管鳞癌进展的作用机制。靶向TAMs的治疗策略已从早期的清除与重编程,拓展至表型重塑、吞噬检查点干预及靶向前体细胞等新兴方向。然而,肿瘤微环境的代偿性与可塑性使得单一靶向策略疗效有限,将TAMs靶向治疗与免疫检查点抑制剂、化疗或抗血管生成药物联合应用,有望逆转免疫抑制、克服临床耐药。未来需借助单细胞测序与空间多组学技术深入解析TAMs异质性,并推动生物标志物与智能药物递送系统的临床转化研究,为优化ESCC治疗策略提供新方向。

     

    Abstract: Tumor-associated macrophages (TAMs) are a key immune population that influences the immunosuppressive microenvironment and drives the malignant progression of esophageal squamous cell carcinoma (ESCC). This review summarizes the mechanisms by which TAMs promote ESCC progression through facilitating tumor proliferation, angiogenesis, metastasis, and therapeutic resistance. TAM-directed therapeutic strategies have progressed from early methods of depletion and reprogramming to emerging directions such as phenotypic remodeling, phagocytic checkpoint intervention, and precursor cell targeting. However, the compensatory nature and plasticity of the tumor microenvironment limit the efficacy of monotherapy. The combination of TAM-targeted therapies with immune checkpoint inhibitors, chemotherapy, or anti-angiogenic agents shows potential for reversing immunosuppression and overcoming clinical resistance. Future efforts should focus on elucidating TAM heterogeneity using single-cell and spatial multi-omics technologies and advancing the clinical use of biomarkers and smart drug delivery systems, thereby providing novel pathways for optimizing therapeutic strategies for ESCC.

     

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