Tumor-associated macrophages (TAM) plasticity and diversity are both essential hallmarks of the monocyte-macrophage lineage and the tumor-derived inflammation. TAM exemplify the perfect adaptable cell with dynamic phenotypic modifications that reflect changes in their functional polarization status. Under several tumor microenvironment (TME)-related cues, TAM shift their polarization, hence promoting or halting cancer progression. Immune checkpoint inhibitors (ICI) displayed unprecedented clinical responses in various refractory cancers; but only approximately a third of patients experienced durable responses. It is, therefore, crucial to enhance the response rate of immunotherapy. Several mechanisms of resistance to ICI have been elucidated including TAM role with its essential immunosuppressive functions that reduce both anti-tumor immunity and the subsequent ICI efficacy. In the past few years, thorough research has led to a better understanding of TAM biology and innovative approaches can now be adapted through targeting macrophages' recruitment axis as well as TAM activation and polarization status within the TME. Some of these therapeutic strategies are currently being evaluated in several clinical trials in association with ICI agents. This combination between TAM modulation and ICI allows targeting TAM intrinsic immunosuppressive functions and tumor-promoting factors as well as overcoming ICI resistance. Hence, such strategies, with a better understanding of the mechanisms driving TAM modulation, may have the potential to optimize ICI efficacy.

肿瘤相关巨噬细胞 (TAM) 的可塑性和多样性是单核细胞-巨噬细胞谱系和肿瘤源性炎症的重要标志。TAM 举例说明了具有动态表型修饰的完美适应性细胞，这些修饰反映了其功能极化状态的变化。在几种与肿瘤微环境 (TME) 相关的线索下，TAM 改变了它们的极化，从而促进或阻止癌症进展。免疫检查点抑制剂 (ICI) 在各种难治性癌症中表现出前所未有的临床反应；但只有大约三分之一的患者经历了持久的反应。因此，提高免疫治疗的反应率至关重要。已经阐明了几种对 ICI 的抗性机制，包括 TAM 的作用及其基本的免疫抑制功能，可降低抗肿瘤免疫和随后的 ICI 功效。在过去几年中，深入的研究使人们对 TAM 生物学有了更好的了解，现在可以通过靶向巨噬细胞的募集轴以及 TME 内的 TAM 激活和极化状态来调整创新方法。其中一些治疗策略目前正在与 ICI 药物相关的几项临床试验中进行评估。TAM 调节和 ICI 之间的这种组合允许靶向 TAM 内在免疫抑制功能和肿瘤促进因子以及克服 ICI 耐药性。因此，这些策略，更好地理解驱动 TAM 调制的机制，