VITAMIN E could boost immunotherapy responses, according to researchers at The University of Texas MD Anderson Cancer Center (MD Anderson), Houston, USA, by stimulating the activity of dendritic cells in the tumour. The research was a combination of retrospective analysis of clinical records and in-depth laboratory studies.
Immune checkpoint inhibitors give lasting responses to numerous patients with cancer; however, not all patients benefit from this type of immunotherapy. In order to improve the outcomes of immunotherapy, researchers would benefit from understanding the mixed responses. Dietary supplements are believed to be beneficial for overall immunity. In order to investigate the connection between supplements and immunotherapy activity, the researchers at MD Anderson carried out a retrospective analysis of clinical data on patients treated with immunotherapy.
According to the results, there was a significant improvement in the survival of patients with melanoma who took vitamin E while on anti-programmed cell death protein 1 or programmed death-ligand 1 checkpoint inhibitors, compared with patients who did not take vitamin E or any other supplements. The findings were replicated in patients with breast, colon, and kidney cancers. Furthermore, the researchers indicated that vitamin E increased the responses to checkpoint inhibitors in immunogenic mouse models of breast cancer and melanoma. They discovered that the models with low levels of tumour-infiltrating dendritic cells did not profit from vitamin E, which meant that the benefits were dependent on the dendritic cells.
The researchers showed that vitamin E binds and blocks the activity of the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) checkpoint directly in dendritic cells, which in turn increases antigen presentation and primes T cells for an anti-tumour immune response. New therapeutic approaches to better the immunotherapy outcomes could be possible based on these results, which may include the combinations of checkpoint inhibitors and other immunotherapies with vitamin E, as well as targeting SHP-1 directly in dendritic cells.
“SHP-1 is an attractive target to effectively activate dendritic cells for the development of potent immunotherapy,” said lead author Xiangliang Yuan, Research Scientist, Molecular and Cellular Oncology, MD Anderson. “This work yielded important insights on the interaction between vitamin E and SHP-1 that will guide us to develop more specific allosteric SHP-1 inhibitors. Compellingly, it appears that unleashing dendritic cells by inhibiting SHP-1 may be an advantageous strategy to enhance anti-tumor immunity.”