Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1

Area of Science:

• Immunology
• Oncology
• Nutritional Science

Background:

• The effect of dietary supplements on cancer immunotherapies like immune-checkpoint therapy (ICT) is largely unknown.
• Vitamin E (VitE) is a popular supplement used during cancer treatment.

Purpose of the Study:

• To investigate the impact of vitamin E on the efficacy of cancer immunotherapies.
• To elucidate the mechanism by which vitamin E affects anti-tumor immunity.

Main Methods:

• Analysis of electronic health records from ICT-treated cancer patients.
• In vivo studies using mouse cancer models.
• Investigation of dendritic cell (DC) function, including receptor binding and protein interactions.
• Genetic inhibition of SHP1 in DCs and DC-derived extracellular vesicles (DC-EVs).

Main Results:

• Patients treated with ICT and vitamin E showed significantly improved survival.
• Vitamin E enhanced ICT efficacy in mouse models by restoring DC function.
• Vitamin E inhibits the DC-intrinsic checkpoint SHP1, enhancing antigen presentation and T-cell immunity.
• Combining vitamin E with DC-recruiting therapies boosted anti-tumor responses in animals.

Conclusions:

• Dietary vitamin E enhances cancer immunotherapy by inhibiting SHP1 in dendritic cells.
• Vitamin E treatment or SHP1 inhibition in DCs/DC-EVs can augment T-cell antitumor immunity.
• Combining vitamin E with therapies that increase DC presence may improve cancer immunotherapy outcomes.