Adjuvant for immunotherapy
Vitamin E increases the effectiveness of immunotherapy through the activation of dendritic cells
Alina Suleymanova, PCR.news
The use of immune checkpoint inhibitors (ICTIS) as immunotherapy does not always lead to a tumor response and depends on the presence of certain proteins (for example, PD-L1) on the membrane of cancer cells. Traditionally, treatment is based on the hypothesis that vitamins mobilize the body's immunity against neoplasms, so patients receive vitamin supplements. However, there is little reliable data on the effectiveness of dietary supplements in cancer.
Evidence of the positive effect of vitamin E on the results of immunotherapy was provided by a team of scientists from the USA, China and Taiwan.
Scientists analyzed electronic medical records of patients with melanoma. It turned out that in patients who took PD-1/PD-L1 inhibitors and vitamin E, the survival rate was increased compared to patients who received multivitamin complexes or did not receive vitamins. Similar results were obtained when analyzing medical records of an independent mixed group of patients with breast, colon and kidney cancer. At the same time, the combination of vitamin E and chemotherapy did not affect the mortality of patients.
In a mouse model of breast cancer, vitamin E also increased the effectiveness of ICTI. In mouse models of melanoma, the result was ambiguous. Vitamin E worked for the B16-GMCSF subline, enhancing the infiltration of cytolytic T cells and reducing lung metastases compared to vitamin-free ICTI. However, if the mice carried melanoma of sublinia B16-F10, which is characterized by a low number of dendritic cells (DC) in the tumor, the addition of vitamin E to ICTI was useless. Scientists have suggested that the antitumor effect of the vitamin depends on DC. They present the antigens of cancer cells to T-lymphocytes, which causes an immune response against the tumor.
The scientists tested the assumption on dendritic cell cultures. The addition of vitamin E to the culture activated DC. With the joint cultivation of DC and T-lymphocytes, vitamin E promoted the proliferation of the latter. The authors found that the vitamin penetrates into DC through the SCARB1 receptor and inhibits tyrosine phosphatase SHP1. This enzyme serves as a DC checkpoint; it regulates toll-like receptors and the response to cytokine signaling.
In vitro deletion of the gene encoding SHP1 using CRISPR-Cas9 duplicated the effect of vitamin E. Moreover, such manipulation enhanced the representation of cancer cell antigen in vesicles secreted by dendritic cells to communicate with T-lymphocytes. The implantation of modified DC in model mice suppressed tumor growth.
In further in vivo experiments, the addition of vitamin E to a combination of anti-cancer vaccines with ICTI or chemotherapy with ICTI increased the number of cytolytic T cells and activated DC in the tumor. This approach also worked with aggressive tumors, such as pancreatic duct adenocarcinoma. In mice that received the vitamin together with therapy, tumor growth was suppressed, symptoms of the disease decreased and life expectancy increased.
The results obtained open up new prospects for the treatment of oncological diseases. According to the researchers, the binding of vitamin E to dendritic cells or their vesicles, as well as the direct inhibition of SHP1 in cells, can become a powerful immunotherapeutic agent.
The article by Yuan et al. Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1 is published in the journal Cancer Discovery.
Portal "Eternal youth" http://vechnayamolodost.ru