Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules ...Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects.Current vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen cross-presentation.Here,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance.The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates autophagy.We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR pathway.The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation.This study presents a paradigm of NIR-II image-guided light-triggered vaccination.The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.展开更多
基金supported in part by grants from National Natural Science Foundation of China(No.81991493,China)Shanghai Municipal Health Commission(No.2022XD045,China)。
文摘Cancer vaccines represent a promising immunotherapeutic treatment modality.The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects.Current vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen cross-presentation.Here,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance.The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates autophagy.We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR pathway.The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation.This study presents a paradigm of NIR-II image-guided light-triggered vaccination.The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.
