Revolutionizing the landscape of hematological malignancy treatment, CAR-T therapies have encountered challenges when applied to solid tumors. The efficacy of T cells is hindered by their limited ability to infiltrate the tumor mass and navigate the hypoxic, immunosuppressive microenvironment, leading to exhaustion. Addressing this limitation, we explore an innovative avenue by harnessing the potential of CAR-bearing phagocytes for the treatment of solid tumors. We have designed a model to unravel the mechanisms underlying the action of CAR-macrophages (CAR-M). Indeed, mononuclear phagocytes emerge as a central player of the polarization of the antitumoral immune response as they combine phagocytic, cytotoxic and antigen-presenting abilities. Using two-photon imaging and a functional probe for phagocytosis, our findings reveal that CAR-M exhibit potency and specificity as phagocytes against diverse tumor types. In vitro experiments demonstrate their ability to control tumor growth. Still, CAR-macrophage’s phagocytic ability is heterogeneous. Understanding the origins of this heterogeneity will allow us to optimize and boost this new promising therapy.
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