Modulating and Imaging Macrophage Reprogramming for Cancer Immunotherapy

Cancer immunotherapy has made great progress in effectively attacking or eliminating cancer. However, the challenges posed by the low reactivity of some solid tumors still remain. Macrophages, as a key component of the tumor microenvironment (TME), play an important role in determining the progression of solid tumors due to their plasticity and heterogeneity. Targeting and reprogramming macrophages in TME to desired phenotypes offers an innovative and promising approach for cancer immunotherapy. Meanwhile, the rapid development of in vivo molecular imaging techniques provides us with powerful tools to study macrophages. In this review, we summarize the current progress in macrophage reprogramming from conceptual roadmaps to therapeutic approaches, including monoclonal antibody drugs, small molecule drugs, gene therapy, and chimeric antigen receptor-engineered macrophages (CAR-M). More importantly, we highlight the significance of molecular imaging in observing and understanding the process of macrophage reprogramming during cancer immunotherapy. Finally, we introduce the therapeutic applications of imaging and reprogramming macrophages in three solid tumors. In the future, the integration of molecular imaging into the development of novel macrophage reprogramming strategies holds great promise for precise clinical cancer immunotherapy.