Johns Hopkins University, Skip Viragh Outpatient Cancer Building, Baltimore, MD, 21287, USA.
Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Semin Immunopathol. 2023 Mar;45(2):187-201. doi: 10.1007/s00281-023-00988-2. Epub 2023 Mar 31.
The complexity and plasticity of the tumor microenvironment (TME) make it difficult to fully understand the intratumoral regulation of different cell types and their activities. Macrophages play a crucial role in the signaling dynamics of the TME. Among the different subtypes of macrophages, tumor-associated macrophages (TAMs) are often associated with poor prognosis, although some subtypes of TAMs can at the same time improve treatment responsiveness and lead to favorable clinical outcomes. TAMs are key regulators of cancer cell proliferation, metastasis, angiogenesis, extracellular matrix remodeling, tumor metabolism, and importantly immunosuppression in the TME by modulating various chemokines, cytokines, and growth factors. TAMs have been identified as a key contributor to resistance to chemotherapy and cancer immunotherapy. In this review article, we aim to discuss the mechanisms by which TAMs regulate innate and adaptive immune signaling in the TME and summarize recent preclinical research on the development of therapeutics targeting TAMs and tumor metabolism.
肿瘤微环境（TME）的复杂性和可塑性使得人们难以充分了解不同细胞类型在肿瘤内的调控及其活性。巨噬细胞在 TME 的信号动态中起着至关重要的作用。在不同的巨噬细胞亚型中，肿瘤相关巨噬细胞（TAMs）通常与预后不良相关，尽管某些亚型的 TAMs 同时可以提高治疗反应性并导致有利的临床结果。TAMs 通过调节各种趋化因子、细胞因子和生长因子，成为癌症细胞增殖、转移、血管生成、细胞外基质重塑、肿瘤代谢以及 TME 中重要的免疫抑制的关键调节剂。TAMs 已被确定为对化疗和癌症免疫治疗产生耐药性的关键因素。在这篇综述文章中，我们旨在讨论 TAMs 调节 TME 中固有和适应性免疫信号的机制，并总结最近针对 TAMs 和肿瘤代谢的治疗靶点的临床前研究。
