Antigen presentation is a core component of the host immune response to cancer vaccines; however, antigen-presenting cells often fail to promote sufficient proliferation of specific T cells, thereby limiting their efficacy. This study demonstrates that by regulating the cholesterol level in the membrane of dendritic cells, the antigen-presenting ability can be enhanced. Based on this discovery, we developed a membrane cholesterol-depleted nanovaccine, aiming to deliver antigens to hepatic steroid cells while reducing membrane cholesterol. Directly depriving membrane cholesterol increased the frequency of cholesterol contact with T cells and reshaped the tumor immune microenvironment to inhibit tumor occurrence and the progression of various tumor models. Mechanistically, the designed nanovaccine promoted the formation of immune synapses in CD8+ T cells and enhanced T cell activation and proliferation by reshaping the cholesterol microdomains in the DC membrane and blocking the cell proliferation pathway, thereby improving the antigen-presenting ability. This study proposes a method to enhance the efficacy of vaccines by reducing the cholesterol level in the membrane of antigen-presenting cells. This study was published in Nature Nanotechnology under the title "Enhancing the Efficacy of Antitumor Nanovaccines through In-Situ Integrated Cholesterol Modulation".
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DOI: 10.1038/s41565-026-02153-w