CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
血液系统恶性肿瘤中的巨噬细胞极化：机制与治疗策略
英文原题：Macrophage polarization in hematologic cancers: mechanisms and therapeutic strategies.
查看英文原题
Macrophage polarization in hematologic cancers: mechanisms and therapeutic strategies.
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中文摘要
白血病治疗面临持续挑战，包括化疗耐药和复发，这凸显了肿瘤微环境（TME）中巨噬细胞极化作为治疗靶点的重要性。巨噬细胞在抗肿瘤 M1 和促肿瘤 M2 表型之间动态转换，其中 M2 极化的肿瘤相关巨噬细胞（TAM）在白血病 TME 中占主导地位。这些细胞分泌 IL-10 和 TGF-β，促进免疫逃逸、血管生成和白血病干细胞（LSC）存活。在 AML 中，M2 TAM 通过 CSF-1/IL-10 信号传导与不良预后和化疗耐药相关。极化受转录因子（STAT6、PPARγ、KLF4）、缺氧和代谢重编程调控。治疗策略聚焦于：(1) M2 清除（抗 CD163/CD206 抗体）；(2) 通路抑制（CCL2/CCR2 或 IL-4/STAT6 阻断）；(3) 代谢调节（糖酵解/OXPHOS 靶向）；以及 (4) 吞噬作用增强（CD47-SIRPα 阻断、HDAC6 抑制）。临床前研究表明，CSF-1R 抑制剂（如 pexidartinib）可破坏 LSC-TAM 串扰，而 CAR-M 疗法与促吞噬 agents 协同作用。尽管存在挑战，巨噬细胞靶向疗法通过重塑 TME、克服耐药和增强免疫治疗，提供了变革性潜力。本综述概述了机制见解和转化策略，以利用巨噬细胞可塑性用于白血病治疗。
展开英文摘要原文
Leukemia treatment faces persistent challenges, including chemotherapy resistance and relapse, highlighting macrophage polarization in the tumor microenvironment (TME) as a therapeutic target. Macrophages dynamically shift between antitumor M1 and protumor M2 phenotypes, with M2-polarized tumor-associated macrophages (TAMs) dominating leukemia TMEs. These cells secrete IL-10 and TGF-β, fostering immune evasion, angiogenesis, and leukemia stem cell (LSC) survival. In AML, M2 TAMs correlate with poor prognosis and chemoresistance via CSF-1/IL-10 signaling. Polarization is regulated by transcription factors (STAT6, PPARγ, KLF4), hypoxia, and metabolic reprogramming.
Therapeutic strategies focus on: (1) M2 depletion (anti-CD163/CD206 antibodies); (2) Pathway inhibition (CCL2/CCR2 or IL-4/STAT6 blockade); (3) Metabolic modulation (glycolysis/OXPHOS targeting); and (4) Phagocytosis enhancement (CD47-SIRPα blockade, HDAC6 inhibition). Preclinical studies demonstrate CSF-1R inhibitors (e. g.
, pexidartinib) disrupt LSC-TAM crosstalk, while CAR-M therapy synergizes with phagocytosis-promoting agents. Despite challenges, macrophage-targeted therapies offer transformative potential by remodeling the TME, overcoming resistance, and augmenting immunotherapy. This review outlines mechanistic insights and translational strategies to harness macrophage plasticity for leukemia treatment.
论文信息
- 作者
- Chen ZG、Yang H、Yang C、Xie YT、Li CM、Xiao T、Wu JH、Gao MY
- 第一作者单位
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, 400037, China.China
- 通讯作者单位
- Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, 400037, China. gaolei7765@tmmu.edu.cn.China
- 文献类型
- 综述
- 期刊
- Blood research2026 Feb 7
- 原文标识
- PubMed 41653356 · DOI 10.1007/s44313-025-00119-w
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