Targeting macrophages in cancer immunotherapy: Frontiers and challenges

作     者：Liu, Yu'e Tan, Huabing Dai, Jingyuan Lin, Jianghua Zhao, Kaijun Hu, Haibo Zhong, Chunlong 

作者机构：Department of Neurosurgery Shanghai East Hospital School of Medicine Tongji University Shanghai 200120 China Department of Pediatric Hematology-Oncology Boston Children's Hospital Dana Farber Cancer Institute Harvard Medical School Boston 02115 MA United States Department of Infectious Diseases Hepatology Institute Renmin Hospital Hubei University of Medicine Shiyan Key Laboratory of Virology Hubei University of Medicine Hubei Province Shiyan 442000 China General internal medicine Wuhan Jinyintan Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan 430048 China School of Computer Science and Information Systems Northwest Missouri State University Maryville 64468 MO United States Department of Cardiothoracic Surgery The Affiliated Huai'an Hospital of Xuzhou Medical University Jiangsu Huai'an China 

出 版 物：《Journal of Advanced Research》 (J. Adv. Res.)

年 卷 期：2025年

基　　金：Key Disciplines Group Construction Project of Shanghai Pudong New Area Health Commission, (PWZxq2022-10) Neuroscience, Innovation and Development Research Project, (YXJL-2022-00351-0183) National Natural Science Foundation of China, NSFC, (81972283) Pudong New Area Health Commission, (PW2022A-28) Medical Discipline Construction Project of Pudong Health Committee of Shanghai, (PWYgy 2021-07) 

主　　题：Cancer immunotherapy CAR macrophage Macrophage polarization Phagocytosis checkpoints 

摘      要：Background: Cancer immunotherapy has emerged as a groundbreaking approach in cancer treatment, primarily realized through the manipulation of immune cells, notably T cell adoption and immune checkpoint blockade. Nevertheless, the manipulation of T cells encounters formidable hurdles. Macrophages, serving as the pivotal link between innate and adaptive immunity, play crucial roles in phagocytosis, cytokine secretion, and antigen presentation. Consequently, macrophage-targeted therapies have garnered significant attention. Aim of review: We aim to provide the most cutting-edge insights and future perspectives for macrophage-targeted therapies, fostering the development of novel and effective cancer treatments. Key scientific concepts of review: To date, the forefront strategies for macrophage targeting encompass: altering their plasticity, harnessing CAR-macrophages, and targeting phagocytosis checkpoints. Macrophages are characterized by their remarkable diversity and plasticity, offering a unique therapeutic target. In this context, we critically analyze the innovative strategies aimed at transforming macrophages from their M2 (tumor-promoting) to M1 (tumor-suppressing) phenotype. Furthermore, we delve into the design principles, developmental progress, and advantages of CAR-macrophages. Additionally, we illuminate the challenges encountered in targeting phagocytosis checkpoints on macrophages and propose potential strategies to overcome these obstacles. © 2024