Manipulating macrophage polarization in cancer patients: From nanoparticles to human chimeric antigen receptor macrophages

Chimeric antigen receptor (CAR) T cell treatment has provided notable results in hematological tumors. Unfortunately, this evidence has not been translated into improved outcomes in solid malignancies so far, where several reports have suggested that T cells encounter substantial difficulties in penetrating and surviving in the tumor microenvironment (TME). Thus, researchers have recently investigated other immune cell types as CAR platforms, in order to overcome the limitations of CAR T cells. Among them, CAR-macrophages (M) technology has emerged as a novel perspective for cancer patients, on the basis of preclinical studies observing that CAR expression in human macrophages could play a crucial role in enhancing phagocytosis, polarizing M2 to M1 phenotype, and stimulating T cell anti-tumor activity. Herein, we provide an overview of current scenario of CAR-Ms in several solid tumors, also focusing on the biological rationale behind this promising therapeutic approach and future research directions in this setting.