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.
Reference: Yuan, X. a. (2022). Vitamin E enhances cancer immunotherapy by reinvigorating dendritic cells via targeting checkpoint SHP1. Cancer discover, 1472-1759.
Many may be wondering how exactly the immune system and cancer are interrelated. It’s quite complex given that it has taken decades of countless scientific research in search of the cure. The goal is to break this cancer into its basic mechanisms to fully understand its totality and appreciate its processes. In general, the immune system works by fighting against any harmful substances such as bacteria, fungi, viruses, and cancer cells. Something important to note is that your own cells and immune system can and will betray you.
Pentoxifylline, sold under the brand name Trental is typically used for vascular disease to increase blood flow due to its effect in reducing blood viscosity. However, there is a gene called c-Rel that is important to maintain the function of regulatory cells such as Tregs and MDSC. As I have discussed, the immune system has two sides, one that is regulatory, which has been tricked by cancer to protect it. There is the other side that can attack cancer.
Our goal is to tip the balance in favor of attacking cancer. In a study published by Grinberg-Bleyer, et al in Cell, Sept 7, 2017, titled “NF-kB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer” they describe how blocking c-Rel can reduce the regulatory function of Tregs. In addition, Li, et al published in Nature Cancer, May 18, 2020, an article titled “c-Rel is a Myeloid Checkpoint for Cancer Immunotherapy” which discusses MDSC.
When it comes to managing the side effects of immunotherapy it is important to be very detailed with observing the symptoms as they can be autoimmune related. With any side effect, if it starts to escalate into something more severe, it is important for the patient to notify the doctor immediately. Below are a couple of the most common side effects or autoimmune-related events experienced by patients who undergo immune checkpoint therapy:
-Skin rash, itching
World Cancer Day has arrived and Williams Cancer Institute would like to thank each and every patient who has entrusted their health with our clinic and treatments. Williams Cancer Institute aims to help create a cancer-free world. Our team has been passionately working on developing continuous medical research to eradicate cancer. We value the courage and strength every cancer patient has, and we honor your resilience.
Immune response in cancer treatments has been studied for over decades and to this day continues to be closely researched in an attempt to provide a less invasive treatment for patients. Thanks to medical research, patients and physicians have access to seventeen immunotherapy FDA approved treatments. This ongoing mission is one of great value and in today’s blog we will be exploring more interesting details about the immune system and cancer.