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Antitumor mechanisms of CAR-macrophage therapy. The antitumor mechanisms of CAR-macrophages can be characterized by four main aspects.(A)CAR-macrophages directly kill tumor cells via antigen-specific phagocytosis mediated by the chimeric antigen receptor. (B)CAR-macrophages exhibit profound interactions with endogenous T cells. On one hand, they present phagocytosed tumor antigens to T cells, and on the other hand, CAR-macrophages may facilitate the activation and persistence of endogenous T cells by costimulation.(C) When employing CD147 as the signaling domain, CAR-macrophages can secrete matrix metalloproteinases (MMPs) that degrade the dense extracellular matrix surrounding solid tumors, thereby facilitating the infiltration of other immune cells.(D)CAR-macrophages exhibit an M1-likephenotype, allowing them to secrete proinflammatory cytokines (e.g., IL-1, IL-6, TNF-α) to educate the tumor microenvironment. (This figure was created at BioRender.com.)
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