Cancer Discovery: Yu Dihua's team found that vitamin E can improve the survival rate of cancer patients, and enhance the effect of cancer immunotherapy by activating dendritic cells

On April 14, 2022, the team of Professor Dihua Yu from MD Anderson Cancer Center published a research paper titled: Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1 in the journal Cancer Discovery

Combining retrospective analysis of clinical records with laboratory studies, the research team found that vitamin E directly binds and blocks the immune checkpoint protein SHP1 in dendritic cells, thereby activating dendritic cell activity, enhancing antigen presentation and priming T cells.

The study suggests new approaches to improve cancer immunotherapy, including combination therapy with vitamin E, or direct targeting of SHP1, which inhibits dendritic cells

"This study broadens our understanding of factors that may influence immunotherapy response," said the study's corresponding author, Dihua Yu, a tenured professor at MD Anderson Cancer Center

Vitamin E linked to improved response to immunotherapy

Immune checkpoint inhibitors are a type of cancer immunotherapy developed in recent years and are considered to be a major breakthrough that has changed the landscape of cancer treatment

Immune checkpoint inhibitors can provide durable therapeutic responses in many cancer patients, but not all cancer patients benefit.

Dietary supplements are thought to boost immunity, but little is known about the effects of dietary supplements on immunotherapeutic activity

The research team found that patients with melanoma who received PD-1/PD-L1 immune checkpoint inhibitors were treated with PD-1/PD-L1 immune checkpoint inhibitors compared to those who did not take vitamin E or multivitamins.

This finding was validated in an independent mixed cohort of breast, colon, and kidney cancer patients

Next, the team found that vitamin E enhanced responses to immune checkpoint inhibitors in mouse models of breast cancer and melanoma

Deciphering the effects of vitamin E on dendritic cells

Dendritic cells are a special type of immune cells that are responsible for presenting antigens to T cells, that is, they play an important role in antigen presentation, which is an important step in the anti-tumor immune response

The research team found that vitamin E treatment led to the upregulation of several activation markers on dendritic cells

Through molecular and structural studies, the research team found that vitamin E can enter dendritic cells and bind to its SHP1 protein.

Further studies have shown that inhibiting the SHP1 gene can mimic the results of vitamin E treatment, increase antigen presentation, and stimulate T cell anti-tumor immune responses

Targeting SHP1 may be a new therapeutic strategy

Since vitamin E appears to improve antigen presentation by dendritic cells, the research team further investigated whether vitamin E could enhance response to therapies known to release tumor antigens and recruit dendritic cell infiltration

Experimental results suggest that vitamin E treatment can enhance the efficacy of cancer vaccines and immunogenic chemotherapy in combination with checkpoint inhibitors, including the treatment of immunotherapy-resistant pancreatic cancer

Dr.
Xiangliang Yuan, the first author of the paper, said that SHP1 is an attractive target to efficiently activate dendritic cells for the development of effective immunotherapies
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This study provides important insights into the interaction between vitamin E and SHP1, which will guide us to develop more specific SHP1 inhibitors, and reactivation of dendritic cell antigen presentation by inhibiting SHP1 may be effective in enhancing antitumor immunity.
strategy
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It is reported that the research team is currently working with clinicians at MD Anderson Cancer Center to evaluate the effect of vitamin E in combination with immune checkpoint inhibitors and other immunotherapies
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In addition, the research team is exploring opportunities to develop SHP1 inhibitors, as well as SHP1-silencing dendritic cells and dendritic cell-derived extracellular vesicles as new future therapeutic options
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Original source:

Xiangliang Yuan, et al.
Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1 .
Cancer Discov candisc.
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2021.