Vitamin E Boost Response of Cancer Immunotherapy

A recent study published by Yuan et al. from MD Anderson Cancer Center showed that natural
Vitamin E (DL-a-tocopherol) enhanced the response rates of cancer immunotherapy by
reinvigorating dendritic cells. I am going to break down the overall key highlights of the study.
One is that they reviewed the electronic health records of cancer patients on immunotherapy
and determined that one’s taking Vitamin E had improved survival. This led them to try to
determine the mechanism in the mouse model. They discovered that Vitamin E entered the
dendritic cells inhibiting a checkpoint within them called SHP1. This resulted in enhanced
antigen presentation; as you may know, dendritic cells are involved in presenting foreign or
tumor antigens to other immune cells, such as T cells, to activate an immune response. There
has been much work on dendritic cell vaccines, which has been disappointing. This is because
that is only one part of the activation of the immune response. In addition, like most immune
cells, dendritic cells can also be regulatory to inhibit an immune response against cancer.
However, in this situation described in the study, Vitamin E leads to an activation of mature
dendritic cells presenting tumor antigen, and the overall response is enhanced due to the
presence of traditional immunotherapy such as PD-1 CTLA-4 inhibitors. In previous studies, the
benefits of Vitamin E were not clear.

Another study to keep in mind was published by Kang et al. in 2014, showing that Vitamin E
reduced myeloid-derived suppressor cells (MDSC) and increased the effects of CD8+ T cells
against tumors; as you may know from my book that MDSCs are immune cells that inhibit the
anti-cancer immune response, essentially protecting cancer. High amounts of MDSC are
associated with a poor prognosis and reduce potential response to immunotherapy. In the
study by Kang, they showed that Vitamin E reduced the MDSCs, resulting in increased anti-
cancer CD8+ T cells infiltrating the tumor. This study gives a different mechanism but adds more
data backing the use of Vitamin E in conjunction with immunotherapy.

Indeed, supplementation with Vitamin E should be considered for patients on immunotherapy
for cancer. However, not much has been discussed on dosing. The 2014 study showed benefits
with dietary Vitamin E, but they also described a much more significant effect when injected
into the tumor. They explain that injected Vitamin E can modify the tumor microenvironment
to be more receptive to other immunotherapy treatments. As you can see, the theme of
injection into the tumor site continues to be the most potent treatment option. Otherwise, a
standard dose of 400 IU of natural Vitamin E orally a day is probably helpful.

Jason R. Williams, MD, DABR

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