Abstract
Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated cancer patients who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DCs). VitE entered DCs via SCARB1 receptor and restored tumor-associated DCs’ functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically, or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and DC-derived extracellular vesicles (DC-EVs) triggering systemic antigen-specific T cell antitumor immunity. Combining VitE with DC-recruiting cancer vaccines, or immunogenic chemotherapies, greatly boosted ICT efficacy in animals. Therefore, combining VitE supplement, or SHP1-inhibited DCs/DC-EVs, with DCs-enrichment therapies could substantially augment T cell antitumor immunity and enhance the efficacies of cancer immunotherapies.