Macrophage-centered therapy strategies: A promising weapon in cancer immunotherapy

Abstract

Macrophages are critical phagocytes in the immune system, and tumor-infiltrating macrophages can substantially influence the efficacy and prognosis of immunotherapy. Therefore, macrophages may serve as therapeutic targets for modulating the tumor immune microenvironment. Macrophage-based drug delivery systems have been extensively evaluated owing to their excellent biocompatibility, long half-life, and inherent ability to migrate and accumulate at sites of inflammation, such as tumors. Live macrophages and their membrane coatings contain abundant receptor proteins that facilitate payload transport across physiological barriers. In this review, we discuss strategies that utilize macrophages as targets and delivery carriers for cancer immunotherapy. Here, we summarize the different macrophage phenotypes, tumor-associated macrophagetargeting strategies, and biomimetic delivery carriers derived from macrophages used in immunotherapy. Overall, macrophage-centered strategies for cancer therapy hold considerable promise for clinical applications.

Keywords

Macrophages / Immunotherapy / Drug delivery system / Membrane coatings / Extracellular vesicles

Conflicts of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Acknowledgments

This manuscript was partially supported by the Foundation of Jilin Science-Technology Committee [20250206003ZP; 20230402042GH, Z.Y.], National Natural Science of China [21HAA01203, Z.Y.; Grant No 82030107, J.G.], and Graduate Innovation Fund of Jilin University (2024CX203, M.S.; 2025CX129, J.C.). The authors would like to thank Yujin Chen, Hainan Overseas Chinese Middle School, Class 29, for assisting with the drawing of the figures. We further acknowledge the support of BioRender.com, which was used to create all the artwork in this manuscript.

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