巨噬细胞是多才多艺和异质性的先天免疫细胞，承担了平衡免疫反应和组织修复以维持稳态的中央作用。一旦恶性增长利用了这种可塑性，就会在肿瘤微环境内编织多层次的相互作用，助长癌症生态系统的演化。在这里，我们回顾了在实体肿瘤中共同支撑和长期塑造肿瘤相关巨噬细胞（TAM）表型状态的多层次影响来源。我们讨论了TAM如何在自然选择、生物扩散和治疗耐药的背景下引导肿瘤演化，响应这些信号。在这篇文章中，提出了一些研究前沿，以在癌症中治疗性地利用TAM的复杂角色。在利用目前应用的TAM靶向策略和使用下一代技术获得的知识的基础上，我们提出了概念性进展和重新调整TAM多方面调节共同进化癌症生态系统的新疗法。Copyright © 2023 Elsevier Inc. All rights reserved.

Macrophages are versatile and heterogeneous innate immune cells undertaking central functions in balancing immune responses and tissue repair to maintain homeostasis. This plasticity, once co-opted by malignant outgrowth, orchestrates manifold reciprocal interactions within the tumor microenvironment, fueling the evolution of the cancer ecosystem. Here, we review the multilayered sources of influence that jointly underpin and longitudinally shape tumor-associated macrophage (TAM) phenotypic states in solid neoplasms. We discuss how, in response to these signals, TAMs steer tumor evolution in the context of natural selection, biological dispersion, and treatment resistance. A number of research frontiers to be tackled are laid down in this review to therapeutically exploit the complex roles of TAMs in cancer. Building upon knowledge obtained from currently applied TAM-targeting strategies and using next generation technologies, we propose conceptual advances and novel therapeutic avenues to rewire TAM multifaceted regulation of the co-evolving cancer ecosystem.Copyright © 2023 Elsevier Inc. All rights reserved.