Two-faced STING
STING Protein May Change Cancer Immunotherapy
The STING protein not only plays an important role in innate immunity, but also participates in the mechanisms of acquired immunity. This, in particular, may affect one of the types of cancer immunotherapy. Scientists from Petrozavodsk State University, the Kurchatov Institute and the M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences together with colleagues from Tufts University and Tufts Medical Center (USA) conducted research within the framework of a project supported by a grant from the Russian Science Foundation, and its results were published in Cutting Edge: The Journal of Immunology (Larkin et al., Cutting Edge: Activation of STING in T Cells Induces Type I IFN Responses and Cell Death).
Stimulator of Interferon Genes (STING) is a transmembrane protein 173 (TMEM173), which in the human body is encoded by the TMEM173 gene and plays an important role in innate immunity. When cells are infected with intracellular viruses and bacteria, STING stimulates the formation of type I interferons (IFN-I), which help regulate the activity of the immune system.
"In this study, it was shown that STING can be activated not only in macrophages, the main cells of the innate immune response, but also in T cells responsible for acquired immunity. Activation of STING in the latter stimulates the production of IFN-I and the expression of ISGs (genes stimulated by interferon), which is characteristic of innate immunity cells. STING activation also causes stress of the endoplasmic reticulum (an organoid that is a branched closed system of membrane tubules) and activation of apoptosis pathways (programmed death), thereby leading to the death of T cells," said Alexander Poltorak, project manager, Candidate of Chemical Sciences, leading researcher at Petrozavodsk State University.
These results force a new look at STING-mediated immune therapy, which is considered a promising model for developing cancer immunotherapy. This approach is based on the fact that antigen–presenting cells activated by special chemicals – agonists - STING from the tumor microenvironment produce IFN-I and subsequently activate the T-cell response against tumor antigens.
"This type of therapy is promising and very effective, including through direct injection of DNA into the tumor. However, the data obtained by us indicate the need to revise STING-targeted immunotherapy, taking into account possible effects on T cells. Thus, DNA-induced cytotoxicity observed in T cells may be an undesirable effect of such therapy or, on the contrary, its goal," the scientist concluded.
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04.07.2017