Vitamin E enhances cancer immunotherapy by reinvigorating dendritic cells via targeting checkpoint SHP1.
Open accessPublished version of a preprint
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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A potential mechanism underlying the association between diet and immunotherapy response is the gut microbiome.
“A potential mechanism underlying the association between diet and immunotherapy response is the gut microbiome.”
From Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma (2023) · cites this paper as [13]
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- Authors
- Yuan, X., Duan, Y., Xiao, Y., Sun, K., Qi, Y., Zhang, Y., Ahmed, Z., Moiani, D., Yao, J., Li, H., Zhang, L., Yuzhalin, A. E., Li, P., Zhang, C., Badu-Nkansah, A., Saito, Y., Liu, X., Kuo, W.-L., Ying, H., Sun, S.-C., Chang, J. C., Tainer, J. A., & Yu, D.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Houston Methodist (US)
- 1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
- Corresponding author
- Yu, Dihua
- ORCID
- Venue
- Cancer Discovery
- Published
- 2022-04-14
- Volume
- 12
- Issue
- 7
- Pages
- 1742-1759
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC9262841
- OpenAlex
- W4223963610
- Cited by
- 130
- References
- 51
- Citations by year
- 2026: 23 · 2025: 36 · 2024: 36 · 2023: 29 · 2022: 6
- FWCI
- 11.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- NIH (R01CA184836, R01CA208213, R01CA231149, P01CA092584, R35CA220430)
- METAVivor research (56675, 58284)
- MD Anderson Duncan Family Institute for Cancer Prevention and Risk Assessment NIH Cancer Center Support Grant (P30CA016672)
- Cancer Prevention Research Institute of Texas (RP180813)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- vitamin E, cancer immunotherapy, dendritic cells, SHP-1, immune checkpoint, scavenger receptor class B type I, tumor antigen cross-presentation, extracellular vesicles, dietary supplements, cancer vaccines, immunogenic chemotherapy, survival
- MeSH terms
- Animals, Dendritic Cells, Immunotherapy, Neoplasms, Vitamin E, Cancer Vaccines, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6
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