肺癌（LC）是全世界最常见的癌症之一。肿瘤相关巨噬细胞（TAM）是肿瘤微环境（TME）的重要组成部分，与肿瘤的发生、发展和转移阶段密切相关。巨噬细胞具有可塑性，在TME中不同信号通路的影响下可以分化成不同的表型和功能。经典激活（M1 样）和替代激活（M2 样）代表巨噬细胞的两种极化状态。 M1巨噬细胞表现出抗肿瘤功能，而M2巨噬细胞被认为支持肿瘤细胞的存活和转移。巨噬细胞极化涉及复杂的信号通路，阻断或调节这些信号通路以增强巨噬细胞的抗肿瘤作用已成为近年来的研究热点。与此同时，关于通过合成和天然药物成分调节 TAM 抗肿瘤表型也有了新的发现。纳米技术可以更好地实现联合治疗和药物的靶向递送，最大限度地提高药物的疗效，同时最大限度地减少副作用。到目前为止，针对重编程 TAM 的各种活性物质的纳米药物已经取得了重大进展。在这篇综述中，我们主要全面概述了 TAM 与 LC 微环境中各种细胞之间的信号串扰。此外，还回顾了针对巨噬细胞的新药和纳米药物递送系统（NDDS）的最新进展。最后，我们讨论了巨噬细胞作为治疗靶点的前景以及临床转化的障碍。版权所有 © 2024 Li, Yuan, Li, He, Shen, Luo, Tai, Li, Deng and Luo.

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages' anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.Copyright © 2024 Li, Yuan, Li, He, Shen, Luo, Tai, Li, Deng and Luo.