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基于肿瘤相关巨噬细胞靶向调控的抗肿瘤策略

Antitumor strategies based on targeted modulation of tumor-associated macrophages

  • 摘要: 肿瘤相关巨噬细胞(tumor-associated macrophages, TAMs)是肿瘤中最丰富的固有免疫细胞,TAMs常表现出抗炎性M2表型,是肿瘤发展、转移和耐药性的关键诱导因素,已经成为肿瘤免疫治疗领域的热门靶标。纳米载体的研究与应用优化了以TAMs为靶点的肿瘤治疗策略,本文根据TAMs的特性与功能,详细阐述了基于TAMs的调控策略,包括TAMs耗竭、抑制TAMs募集和TAMs复极化;同时,为了更高效地应用上述策略并克服治疗中常见的脱靶问题,分析了基于纳米载体的TAMs特异性靶向治疗策略,包括被动靶向至TAMs、巨噬细胞主动靶向策略以及M2-TAMs特异性主动靶向策略;最后,针对单独靶向TAMs疗法的局限性,介绍了纳米递送系统同时靶向TAMs和肿瘤细胞的新型治疗策略,为该策略在肿瘤免疫治疗以及与其他疗法联合治疗中的应用提供新思路。

     

    Abstract: Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in tumors, which generally exhibit anti-inflammatory M2 phenotypes, and are the key inducers of tumor development, metastasis and drug resistance, and thus becoming a popular target in the field of antitumor immunotherapy.The study and application of nanocarriers optimize TAMs-targeted antitumor therapy.According to the characteristics and functions of TAMs, modulation strategies based on TAMs are elaborated, including TAMs depletion, inhibition of TAMs recruitment and TAMs repolarization.At the same time, in order to apply the above strategies more efficiently and overcome the general off-target problems in treatment, specific TAMs-targeted therapies based on nanocarriers are reviewed and analyzed, including passive targeting to TAMs, active targeting to macrophages and specifically active targeting to M2-TAMs. Finally, based on the limitations of targeting TAMs alone, new therapeutic strategies of targeting both TAMs and tumor cells via nanocarrier based delivery systems are introduced to provide new ideas for the application of these strategies in the field of tumor immunotherapy and combination therapy with other antitumor strategies.

     

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