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 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), 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 DC-enrichment therapies could substantially augment T-cell antitumor immunity and enhance the efficacy of cancer immunotherapies. SIGNIFICANCE: The impacts of nutritional supplements on responses to immunotherapies remain unexplored. Our study revealed that dietary vitamin E binds to and inhibits DC checkpoint SHP1 to increase antigen presentation, prime antitumor T-cell immunity, and enhance immunotherapy efficacy. VitE-treated or SHP1-silenced DCs/DC-EVs could be developed as potent immunotherapies. This article is highlighted in the In This Issue feature, p. 1599.
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Authors | Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Yuan Zhang, Zamal Ahmed, Davide Moiani, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C Chang, John A Tainer, Dihua Yu |
Journal | Cancer discovery
(Cancer Discov)
Vol. 12
Issue 7
Pg. 1742-1759
(07 06 2022)
ISSN: 2159-8290 [Electronic] United States |
PMID | 35420681
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | ©2022 American Association for Cancer Research. |
Chemical References |
- Cancer Vaccines
- Vitamin E
- Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Topics |
- Animals
- Cancer Vaccines
(therapeutic use)
- Dendritic Cells
- Immunotherapy
- Mice
- Neoplasms
(drug therapy)
- Protein Tyrosine Phosphatase, Non-Receptor Type 6
- Vitamin E
(metabolism)
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