Antibody-dependent cellular phagocytosis in cancer immunotherapy: research and perspectives

Cancer immunotherapy has revolutionized the clinical management of cancer due to its promising survival benefits. Although FDA-approved cancer immunotherapy primarily leverages adaptive immunity for therapeutic efficacy, the critical role of innate immunity in tumor surveillance and eradication has been increasingly recognized. Recently, with the deepening of research in this field, macrophages have emerged as key effectors of the innate anti-tumor response, with antibody-dependent cellular phagocytosis (ADCP) becoming one of the primary mechanisms involved in cancer immunotherapy. As such, exploring ADCP-inducing monoclonal antibodies (mAbs) as forefront therapeutic regimens for patients with cancer is therefore highly sought after. Here, we broadly summarize recent translational advances in harnessing macrophage phagocytosis as a pivotal therapeutic approach in cancer immunotherapy, especially addressing how intravital imaging sheds light on ADCP in a real-time manner. Moreover, various challenges for targeting phagocytosis, strategies to enhance ADCP, and factors limiting its efficiency have also been summarized. We also investigated the potential of chimeric antigen receptor (CAR) macrophages as a next-generation therapeutic modality that bridges the innate and adaptive immune systems to induce robust anti-tumor immune responses. The insights presented in this review will set the scene for future investigations of possible alternative approaches that consider the antibody-dependent cellular phagocytosis for improved cancer immunotherapy.