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Immune checkpoint inhibitors are first-line drugs for cancer treatment; however, some patients eventually develop drug resistance. Recent studies have revealed that dendritic cells (DCs) play a pivotal role in the refractory checkpoint blockade therapy, while the aryl hydrocarbon receptor (AhR) is closely associated with immune activation.

The team led by Dr. Yungling Leo Lee has developed a DC-targeted liposomal delivery system (SP65-lipo-CH) that precisely delivers an AhR inhibitor into DCs. This targeted approach effectively activates the IL12–IFNγ axis, enhances the tumor-killing activity of natural killer cells, and downregulates the expression of PD-L1 on the surface of DCs. Using colon cancer and orthotopic lung cancer mouse models, the team also demonstrated that this nanomedicine significantly suppressed tumor growth and prolonged survival. The innovative liposomal platform not only highlights the importance of DC-mediated immunity in refractory checkpoint blockade therapy, but also provides a promising strategy for infectious diseases and cancer immunotherapy.

This research was supported by the Biotechnology Research Park Translational (BRPT) Project, with assistance from the ASCORE, Inflammation Core Facility, and Taiwan Mouse Clinic from Academia Sinica, as well as IBMS Common Equipment Core. The study was published on October 15, 2025, in Journal of Nanobiotechnology.