biostudies-literatureYuan XMETAVivor researchMD Anderson Duncan Family Institute for Cancer Prevention and Risk Assessment NIH Cancer Center Support GrantNCI NIH HHSCancer Prevention Research Institute of TexasNIH1742-1759https://www.ebi.ac.uk/biostudies/studies/S-EPMC9262841biostudies-literatureUnknown12(7)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 patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC 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-EV),Cancer discoveryVitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1.PMC9262841P30CA016672R35CA220430P01CA092584R01 CA184836R01CA231149R35 CA22043058284R01 CA231149R01CA184836P30 CA016672RP18081356675R01 CA208213P01 CA092584R01CA208213Li HYuzhalin AESun SCYao JAhmed ZBadu-Nkansah ASaito YXiao YLi PYu DZhang LYing HKuo WLLiu XTainer JAZhang YQi YYuan XMoiani DZhang CChang JCDuan YSun KfalseVitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1.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 patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC 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-EV),2022-01-01T00:00:00Z2022 Jul2026-05-09T22:19:05.087Z2025-04-06T14:11:17.465ZS-EPMC92628413542068110.1158/2159-8290.cd-21-090010.1158/2159-8290.CD-21-0900