Bacteria-mimicking cancer cells reprogram macrophages via multiple PRR pathways for cancer immunotherapy

Although macrophages are a powerful cell-based platform for cancer immunotherapy, their antitumor functions, such as phagocytosis and inflammatory responses, are limited by the immunosuppressive tumor microenvironment. Here, we show that decorating cancer cell membranes with bacteria-derived pathogen-associated molecular patterns (PAMPs) initiates phagocytosis and inflammatory responses of macrophages toward cancer cells involving various pattern recognition receptor signaling. Membrane-attached PAMP nanoparticles maintained their immunostimulatory functions. The phagocytic macrophage fraction increased when coincubated with membrane-decorated cancer cells, along with an increased secretion of inflammatory cytokines. Transcriptome analysis revealed that the response of macrophages to PAMP-decorated cancer cells resembled their response to bacteria. In a mouse model, locally injected membrane-decorating PAMP nanoparticles suppressed tumor growth, and the effect was enhanced in combination with the chemotherapeutic drug doxorubicin. Our findings provide insights into the use of macrophages as a cancer immunotherapy modality.