肿瘤微环境对巨噬细胞极化调控的研究进展

Advances in the regulation of macrophage polarization by the tumor microenvironment.

作者信息

Peng Minzhi, Zhu Yuan, Hu Yi, Wen Jianping, Huang Weiguo

机构信息

Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, 541199, China.

Oncology Department of the People's Hospital of Changshou Chongqing, Chongqing, 401220, China.

出版信息

Discov Oncol. 2025 Aug 6;16(1):1487. doi: 10.1007/s12672-025-03258-9.

Abstract

The tumor microenvironment (Tumor Microenvironment, TME) is a core regulatory factor in the occurrence, development, and treatment resistance of tumors. Macrophages, as key immune cell components in the TME, have a profound impact on the tumor process (Visser and Joyce in Cancer Cell 41:374-403, 2023). This review aims to systematically elucidate the characteristics and functional differences of macrophage polarization into M1 and M2 phenotypes within the TME. Additionally, it endeavors to dissect the regulatory mechanisms by which metabolic products, cytokines, and extracellular matrix components secreted by tumor cells modulate macrophage polarization (Wang et al. in Mol Cancer 23:268, 2024). Moreover, the metabolic reprogramming of tumorassociated macrophage (TAM) is a core mechanism for their functional shift, and intervening in metabolic pathways holds promise for reprogramming TAMs to inhibit tumor progression (Jin et al. in Nat Cancer 6:239-252, 2025). Within the TME, macrophages can be polarized into classically activated M1 and alternatively activated M2 types (Ge and Wu in Zhongguo Fei Ai Za Zhi 26:228-237, 2023). Accumulating evidence indicates that classically activated M1 macrophages orchestrate anti-tumor immunity by secreting pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12), which collectively activate cytotoxic T lymphocyte responses, induce tumor cell apoptosis, and enhance immune surveillance (Luo et al. in Front Immunol 15:1352946, 2024). In contrast, M2 macrophages are induced in the TME and promote tumor angiogenesis, immune evasion, tumor cell proliferation, and metastasis by secreting factors such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) (Wang et al. in NPJ Precis Oncol 8:31, 2024). Therefore, in-depth research on the mechanisms of macrophage polarization in the tumor microenvironment provides an important basis for developing new tumor immunotherapy strategies and has significant clinical translational value.

摘要

肿瘤微环境(Tumor Microenvironment, TME)是肿瘤发生、发展及治疗抵抗的核心调节因子。巨噬细胞作为TME中的关键免疫细胞成分,对肿瘤进程有深远影响(Visser和Joyce,发表于《癌细胞》41:374 - 403,2023年)。本综述旨在系统阐明TME中巨噬细胞极化为M1和M2表型的特征及功能差异。此外,还试图剖析肿瘤细胞分泌的代谢产物、细胞因子和细胞外基质成分调节巨噬细胞极化的调控机制(Wang等人,发表于《分子癌症》23:268,2024年)。而且,肿瘤相关巨噬细胞(TAM)的代谢重编程是其功能转变的核心机制,干预代谢途径有望重编程TAM以抑制肿瘤进展(Jin等人,发表于《自然癌症》6:239 - 252,2025年)。在TME中,巨噬细胞可极化为经典激活的M1型和替代激活的M2型(Ge和Wu,发表于《中国肺癌杂志》26:228 - 237,2023年)。越来越多的证据表明,经典激活的M1巨噬细胞通过分泌促炎细胞因子来协调抗肿瘤免疫,这些细胞因子包括肿瘤坏死因子-α(TNF-α)和白细胞介素-12(IL-12),它们共同激活细胞毒性T淋巴细胞反应、诱导肿瘤细胞凋亡并增强免疫监视(Luo等人,发表于《前沿免疫学》15:1352946,2024年)。相比之下,M2巨噬细胞在TME中被诱导,并通过分泌血管内皮生长因子(VEGF)和转化生长因子-β(TGF-β)等因子促进肿瘤血管生成、免疫逃逸、肿瘤细胞增殖和转移(Wang等人,发表于《NPJ精准肿瘤学》8:31,2024年)。因此,深入研究肿瘤微环境中巨噬细胞极化的机制为开发新的肿瘤免疫治疗策略提供了重要依据,具有重大的临床转化价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47c6/12328869/44107cf735eb/12672_2025_3258_Fig1_HTML.jpg

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