Abstract Macrophages are prevalent in multiple tumors and exhibit diverse and potent functional activities. Therapeutic reprogramming of macrophage phenotypes represents a promising strategy for cancer immunotherapy. Engineering chimeric antigen receptors (CARs) to endow macrophages with anti‐tumor capacities demonstrated encouraging efficacy, particularly in enhancing tumor‐targeted phagocytosis. Furthermore, CAR macrophages (CAR‐Ms) orchestrate adaptive immunity through secreting pro‐inflammatory cytokines and presenting tumor antigens, thereby activating cytotoxic T lymphocyte responses. These multifaceted properties establish CAR‐Ms as potent immunotherapeutic agents against therapy‐refractory solid malignancies. Herein, we delineate the design principles, recent research advances, and rational combination strategies of CAR‐Ms, with particular emphasis on emerging clinical evidence from ongoing CAR‐M trials. We also explore potential applications of CAR‐Ms in non‐tumorous diseases and forecast future trends based on CAR‐T therapy evolution. CAR‐M development, combined with emerging technologies, will generate new perspectives for advancing cancer immunotherapy.
Wang et al. (2025) studied this question.