The results lead to a possible new therapeutic approach to improve immunotherapy outcomes, including combinations with vitamin E, as well as directly targeting SHP1 in dendritic cells.
Researchers at The University of Texas MD Anderson Cancer Center have found that vitamin E can enhance immunotherapy responses by stimulating the activity of dendritic cells in the tumor, according to findings published in Cancer Discovery.
The researchers found that vitamin E directly binds and blocks the activity of the SHP1 checkpoint protein in dendritic cells, which increases antigen presentation and primes T cells for an anti-tumor immune response. Further, the results lead to a possible new therapeutic approach to improve immunotherapy outcomes, including combinations with vitamin E, as well as directly targeting SHP1 in dendritic cells.
“This study broadens our understanding of factors that can influence responses to immunotherapies,” said corresponding author Dihua Yu, MD, PhD, chair ad interim of Molecular & Cellular Oncology, in a press release. “We demonstrated that vitamin E can reinvigorate dendritic cell antigen presentation via the inhibition of SHP1. These results indicate that vitamin E-treated or SHP1-silenced dendritic cells and dendritic cell-derived extracellular vesicles could be developed as potent immunotherapies for future clinical applications.”
The research team performed a retrospective analysis of clinical data from patients treated at MD Anderson with immunotherapy. Patients with melanoma who took vitamin E while on anti-PD-1/PD-L1 checkpoint inhibitors had significantly improved survival outcomes compared to patients who did not take vitamin E or multivitamins. However, patients who took vitamin E while being treated with chemotherapy did not experience the same benefits, which suggests that the effects were unique to chemotherapy, according to the investigators.
Following this, the researchers demonstrated that vitamin E enhanced responses to checkpoint inhibitors in immunogenic mouse models of breast cancer and melanoma. The models with low levels of tumor-infiltrating dendritic cells did not benefit from vitamin E, which suggests the effects were dependent on these cells, according to the study authors.
Dendritic cells are described as a specific class of immune cells responsible for presenting abnormal proteins, or antigens, to prime T cells, which is a major step in the anti-tumor immune response. With this, tumor-associated dendritic cells can become dysfunctional due to suppressive signals in the tumor microenvironment.
The research team found that vitamin E enters dendritic cells and binds to the SHP1 protein to block its activity and enhance dendritic cells’ functionality to prime T cells. Further, they investigated whether vitamin E could enhance responses from therapies known to release tumor antigens and recruit dendritic cell infiltration.
The researchers are currently exploring opportunities with clinical collaborators at MD Anderson to prospectively evaluate the effects of vitamin E in combination with checkpoint inhibitors and other immunotherapies. They are also analyzing different opportunities to develop a targeted SHP1 inhibitor as well as SHP1-modified dendritic cells and dendritic cell-derived extracellular vesicles as future therapeutic options.
Vitamin E can boost immunotherapy responses by reinvigorating dendritic cells. MD Anderson Cancer Center. April 14, 2022. Accessed April 19, 2022. https://www.mdanderson.org/newsroom/study-finds-vitamin-e-can-boost-immunotherapy-responses.h00-159538956.html