Liu Yu'e, Tan Huabing, Dai Jingyuan, Lin Jianghua, Zhao Kaijun, Hu Haibo, Zhong Chunlong
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, MA 02115, USA.
Department of Infectious Diseases, Hepatology Institute, Renmin Hospital, Hubei University of Medicine, Shiyan Key Laboratory of Virology, Hubei University of Medicine, Shiyan, Hubei Province 442000, China; General internal medicine, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430048, China.
J Adv Res. 2025 Jan 6. doi: 10.1016/j.jare.2024.12.043.
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.
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.
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.
癌症免疫疗法已成为癌症治疗中的一种开创性方法，主要通过对免疫细胞的操控来实现，特别是T细胞改造和免疫检查点阻断。然而，T细胞的操控面临巨大障碍。巨噬细胞作为先天性免疫和适应性免疫之间的关键纽带，在吞噬作用、细胞因子分泌和抗原呈递中发挥着关键作用。因此，针对巨噬细胞的疗法备受关注。
我们旨在为针对巨噬细胞的疗法提供最前沿的见解和未来展望，推动新型有效癌症治疗方法的发展。
迄今为止，针对巨噬细胞的前沿策略包括：改变其可塑性、利用嵌合抗原受体巨噬细胞（CAR-巨噬细胞）以及靶向吞噬检查点。巨噬细胞具有显著的多样性和可塑性，提供了一个独特的治疗靶点。在此背景下，我们批判性地分析了旨在将巨噬细胞从M2（促肿瘤）表型转变为M1（抑肿瘤）表型的创新策略。此外，我们深入探讨了CAR-巨噬细胞的设计原则、发展进展和优势。此外，我们阐明了在靶向巨噬细胞吞噬检查点时遇到的挑战，并提出了克服这些障碍的潜在策略。
