Gu Ming, Liu Yang, Zheng Wenhui, Jing Zuoqian, Li Xiang, Guo Wei, Zhao Zimo, Yang Xu, Liu Zhe, Zhu Xinwang, Gao Wei
Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
Semin Cancer Biol. 2024 Nov;106-107:43-57. doi: 10.1016/j.semcancer.2024.08.006. Epub 2024 Aug 29.
Lung cancer is one of the most common cancers worldwide and a leading cause of cancer-related deaths. Macrophages play a key role in the immune response and the tumour microenvironment. As an important member of the immune system, macrophages have multiple functions, including phagocytosis and clearance of pathogens, modulation of inflammatory responses, and participation in tissue repair and regeneration. In lung cancer, macrophages are considered to be the major cellular component of the tumor-associated inflammatory response and are closely associated with tumorigenesis, progression and metastasis. However, macrophages gradually undergo a senescence process with age and changes in pathological states. Macrophage senescence is an important change in the functional and metabolic state of macrophages and may have a significant impact on lung cancer development. In lung cancer, senescent macrophages interact with other cells in the tumor microenvironment (TME) by secreting senescence-associated secretory phenotype (SASP) factors, which can either promote the proliferation, invasion and metastasis of tumor cells or exert anti-tumor effects through reprogramming or clearance under specific conditions. Therefore, senescent macrophages are considered important potential targets for lung cancer therapy. In this paper, a systematic review of macrophages and their senescence process, and their role in tumors is presented. A variety of inhibitory strategies against senescent macrophages, including enhancing autophagy, inhibiting SASP, reducing DNA damage, and modulating metabolic pathways, were also explored. These strategies are expected to improve lung cancer treatment outcomes by restoring the anti-tumor function of macrophages.
肺癌是全球最常见的癌症之一，也是癌症相关死亡的主要原因。巨噬细胞在免疫反应和肿瘤微环境中起关键作用。作为免疫系统的重要成员，巨噬细胞具有多种功能，包括吞噬和清除病原体、调节炎症反应以及参与组织修复和再生。在肺癌中，巨噬细胞被认为是肿瘤相关炎症反应的主要细胞成分，与肿瘤发生、进展和转移密切相关。然而，巨噬细胞会随着年龄增长和病理状态的变化逐渐经历衰老过程。巨噬细胞衰老在巨噬细胞的功能和代谢状态方面是一个重要变化，可能对肺癌发展产生重大影响。在肺癌中，衰老的巨噬细胞通过分泌衰老相关分泌表型（SASP）因子与肿瘤微环境（TME）中的其他细胞相互作用，这些因子在特定条件下既可以促进肿瘤细胞的增殖、侵袭和转移，也可以通过重编程或清除发挥抗肿瘤作用。因此，衰老的巨噬细胞被认为是肺癌治疗的重要潜在靶点。本文对巨噬细胞及其衰老过程以及它们在肿瘤中的作用进行了系统综述。还探索了多种针对衰老巨噬细胞的抑制策略，包括增强自噬、抑制SASP、减少DNA损伤和调节代谢途径。这些策略有望通过恢复巨噬细胞的抗肿瘤功能来改善肺癌治疗效果。
