Targeting macrophages in cancer immunotherapy: Frontiers and challenges

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.