REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1679271
Emerging Macrophage-Based Therapies for Cancer: A Review of Preclinical and Clinical Advances
Provisionally accepted
- Szkola Glowna Gospodarstwa Wiejskiego w Warszawie, Warsaw, Poland
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Macrophages, the most abundant immune cells in many solid tumors, are no longer viewed solely as accomplices of cancer but as powerful therapeutic allies. This review charts the rapid rise of macrophage-based immunotherapies, from CD47/SIRPα checkpoint blockade and CAR-macrophages to macrophage-drug conjugates (MDCs). We emphasize emerging frontiers - RNA-based reprogramming, epigenetic modulation, small activating RNA and circRNA approaches, and macrophage-derived extracellular vesicles - that are redefining how tumor-associated macrophages can be targeted or harnessed. Distinct from earlier TAM reviews, we integrate outcomes from ongoing and completed clinical trials, highlight therapeutic platforms beyond classical depletion and polarization, and frame macrophages not only as targets but also as delivery vehicles. By spotlighting both innovative strategies and the challenges of moving them into the clinic, we aim to provide a forward-looking guide for researchers and clinicians shaping the next generation of cancer immunotherapy.
Keywords: Macrophages, Tumor Microenvironment, Immunotherapy, Cancer, cell therapy
Received: 04 Aug 2025; Accepted: 16 Sep 2025.
Copyright: © 2025 Brancewicz and Kucharzewska. 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: Jan Brancewicz, j.brancewicz@cellis.eu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.