Macrophage Extracellular Traps in Immunity and Cancer

Abstract

Macrophage extracellular Traps (METs) are web-like structures released by activated macrophages, composed of a DNA backbone decorated with various proteins. Their core function lies in entrapping and restricting pathogen dissemination, representing an important innate immune defense mechanism of macrophages. Through the activation of multiple inflammatory factors and protein components, METs amplify the inflammatory cascade and are detected in various inflammatory conditions. Moreover, recognizing chronic inflammation as a major oncogenic driver, the role of METs in cancer is increasingly appreciated. By fostering an immunosuppressive tumor microenvironment and degrading the extracellular matrix, METs facilitate epithelial-mesenchymal transition, thereby promoting angiogenesis and tumor cell survival. In addition, METs affect the efficacy of cancer immunotherapy. While METs antagonize cancer immunotherapy by creating a physical barrier and fostering immunosuppression, their intrinsic cytotoxicity and ability to amplify inflammatory signals also synergize with immune-activating strategies. This review comprehensively examines the underlying function of METs in immunity, tumorigenesis, and cancer immunotherapy. Deciphering these functional connections will provide critical insights for targeting METs to enhance the efficacy of cancer immunotherapies. © 2026 The Author(s). Advanced Science published by Wiley-VCH GmbH.