巨噬细胞作为最丰富的肿瘤内浸润细胞之一，在肿瘤的发展和转移过程中扮演着重要角色。肿瘤相关巨噬细胞（TAM）的频率和极化与疾病进展、肿瘤转移以及对各种治疗的抵抗性相关。炎症性M1巨噬细胞具有吞噬肿瘤细胞的潜力。相反，抗炎性M2巨噬细胞在肿瘤中占主导地位，促进肿瘤进展和免疫逃逸。调控肿瘤免疫微环境，改善肿瘤相关的免疫抑制并引发抗肿瘤免疫反应的一种策略是靶向巨噬细胞。调整TAM的极化状态、清除TAM和阻断抑制性信号是肿瘤治疗方面具有巨大潜力的策略。此外，基于巨噬细胞的仿生载体被广泛研究，目的在于延长循环时间、增强肿瘤靶向递送和减少治疗药物的免疫原性，以提高治疗效果。此外，通过基因工程将嵌合抗原受体（CAR）导入巨噬细胞，使其能够识别肿瘤抗原并执行肿瘤细胞特异性吞噬。这些策略将丰富用于治疗肿瘤的工具箱，特别是固体肿瘤、耐药肿瘤和转移性肿瘤。在此，我们介绍巨噬细胞在肿瘤进展中的作用，总结了巨噬细胞为中心的抗癌治疗的最新进展，并讨论其挑战以及未来的应用。图形摘要。© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.

Macrophages, as one of the most abundant tumor-infiltrating cells, play an important role in tumor development and metastasis. The frequency and polarization of tumor-associated macrophages (TAMs) correlate with disease progression, tumor metastasis, and resistance to various treatments. Pro-inflammatory M1 macrophages hold the potential to engulf tumor cells. In contrast, anti-inflammatory M2 macrophages, which are predominantly present in tumors, potentiate tumor progression and immune escape. Targeting macrophages to modulate the tumor immune microenvironment can ameliorate the tumor-associated immunosuppression and elicit an anti-tumor immune response. Strategies to repolarize TAMs, deplete TAMs, and block inhibitory signaling hold great potential in tumor therapy. Besides, biomimetic carriers based on macrophages have been extensively explored to prolong circulation, enhance tumor-targeted delivery, and reduce the immunogenicity of therapeutics to augment therapeutic efficacy. Moreover, the genetic engineering of macrophages with chimeric antigen receptor (CAR) allows them to recognize tumor antigens and perform tumor cell-specific phagocytosis. These strategies will expand the toolkit for treating tumors, especially for solid tumors, drug-resistant tumors, and metastatic tumors. Herein, we introduce the role of macrophages in tumor progression, summarize the recent advances in macrophage-centered anticancer therapy, and discuss their challenges as well as future applications. Graphical abstract.© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.