MINI REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1658795
This article is part of the Research TopicImmune Landscape in the Transition from Inflammation to TumorigenesisView all 5 articles
Progress in targeting tumor-associated macrophages in cancer immunotherapy
Provisionally accepted
- 1Department of Gynaecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China, Harbin, China
- 2Capital Medical University, No. 10 Xitoutiao, outside You'anmen, Fengtai District, Beijing,100069, China, Beijing, China
- 3Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China, Harbin, China
- 4Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, 150081, China, Harbin, China
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Tumor-associated macrophages (TAMs) are central to tumor progression, immune suppression, and resistance to therapy, making them promising targets in cancer immunotherapy. TAMs exhibit functional heterogeneity, polarizing into pro-tumor (M2-like) and anti-tumor (M1-like) phenotypes under different microenvironmental cues. M2-like TAMs promote immune evasion, angiogenesis, and metastasis, while M1-like TAMs enhance antitumor immunity. Combining TAM-targeted therapies with immune checkpoint inhibitors is also emerging as a potential strategy to enhance immunotherapy efficacy. This review outlines TAM-mediated immunosuppression mechanisms, including the secretion of VEGF, TGF-β, and immune checkpoint molecules like PD-L1. We also summarize the current strategies targeting TAMs, such as blocking the CD47/SIRPα axis, using CD40 agonists, and PI3Kγ inhibitors, which have shown promise in preclinical studies. Overall, this review underscores TAMs as pivotal therapeutic targets and proposes future directions to optimize combinatorial immunotherapy for enhanced clinical outcomes.
Keywords: Tumor-associated macrophages, Tumor Microenvironment, Immunosuppression, immune checkpoints, treatment resistance, Immunotherapy
Received: 03 Jul 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Xia, Zhang, Wang, Huang, Guo and Lei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xinyu Guo, Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China, Harbin, China
Fang Lei, Department of Gynaecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China, Harbin, China
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