Engineered macrophages with IL-10-TLR9 signal switch receptors for reprogramming tumor microenvironment and enhancing antitumor immunity - Experimental & Molecular Medicine

Researchers described an engineered macrophage approach in Experimental & Molecular Medicine that uses a “signal switch” receptor to turn IL-10—described as a prevalent immunosuppressive cytokine in solid tumors—into pro-inflammatory activity within tumor tissue. The team created a CAR-like switch receptor construct (SR CAR) fusing the IL-10 receptor exodomain to the TLR9 receptor endodomain, producing SR CAR-M, which converts IL-10 signals into activation of the TLR9 pathway. In experiments, SR CAR-M cells showed an M1-like phenotype, stronger phagocytosis and cytotoxicity, improved resistance to microenvironmental reprogramming, and improved stimulation of DC maturation and T-cell activation. The study also reports dual-functional SR CAR-M secreting anti-PD-L1 antibodies (SRPα CAR-M), with improved tumor control in an orthotopic 4T1 breast cancer model. The paper includes detailed cell culture and assay methods, listing multiple cell lines and growth media.