The study provides new strategies to improve the effectiveness of clinical T-cell therapy.

The team study by Deng Liufu, a researcher at the Institute ofImmunologyin Shanghai, reveals that endogenous cGAS-STING signals promote the mechanism of the immune response of T-cells anti-
tumor
by maintaining the "dryness" of CD8-T cells, and provides a new strategy and basis for improving the effectiveness of clinical T-cell therapyThe results of the study were recently published in Science-Translational Medicineimmunotherapy is a hot topic in the field of tumor therapy, and T-cell-based immunotherapy has encountered multiple challenges in eradicating solid tumorsThe biggest advantage of T-cell therapy is its specific identification of tumor antigens, which effectively kills tumor cells to preventtumorimmune escapeHowever, continuous antigen stimulation can lead to T-cell depletion, increased surface inhibitory receptors (e.gPD-1, etc.) and decreased effect functionCurrently, exhausted T-cells can be "resurrected with full blood" by blocking the PD-1 pathway, but the strategy is still limited by the quality of T-cellsTherefore, how to improve the quality of T cells to keep immunotherapy T cells longer, prompting them to replicate and amplification is a new strategy to improve the effectiveness of T-cell therapycGAS (cyclic GMP-AMP synthase)-STING pathway is an important way to initiate the natural immune response of anti-tumor, and is expected to become a new generation of immunotherapy targets for tumors from "cold" to "hot"At present, the research on cGAS-STING pathway is mainly focused on tumor cells and natural immune cells, and it is found that it plays a very important role in tumor immunity, cell aging, inflammatory diseases and viral infection, but little is known about the changes of cGAS-STING pathways in T cells, especially in tumor microenvironment 's Team Deng Liufu found that cGAS and STING were significantly reduced in peripheral blood CD8 plus T cells in cancer patients, suggesting that cGAS and STING were important for CD8 plus T cells The application of T-cell back-to-the-mouse tumor models showed that cGAS and STING deficiency in CD8 plus T cells weakened the effectiveness of T-cells in the treatment of tumors The researchers further used genetic , pharmacological tools, and blocking antibodies to interfere with cGAS-STING and type I interferon signals, demonstrating that this pathway is essential for maintaining anti-tumor stem cells -like CD8-t cells and the best anti-tumor response It was found that cGAS and STING affected the "dryness" of depleted CD8 plus T cells in tumor microenvironmentby by regulating the expression of TCF1 and Slamf6 The cGAS-STING-mediated type I interferon signal enhances the differentiation of stem cells in the form of self-secretion, cd8-T cells, and blocks the production of effect factors by inhibiting the activity of Akt In addition, in vivo or in vitro stimulation, genomic DNA selectively enriches in the plasma of CD8 plus T cells, which is the key to the activation of the cGAS-STING pathway in T cells There is also such a group of cells in the peripheral blood of human seis, both the characteristics of memory cells, but also the characteristics of stem cells , named stem cell-memory t cells (Tscm), the proliferation of these cells and anti-
tumor activity is the strongest in all T-cell subgroups The study found that STING agonisant diABZI-C3 promoted the differentiation of Nave T cells in peripheral blood in healthy volunteers and cancer patients into Tscm subgroups Even more exciting is the further application of humanized mouse models to find that STING agonists can significantly improve the efficiency of CAR-T cells in treating A549 solid tumors team used Sun Wukong in "The Journey to the West" to portray the findings That is, on the way west, in order to reduce the demons (
tumors cells), Sun Wukong (CD8 plus T cells) need strapping spells of the magic force (STING) and the magic of the eyes of the fire (cGAS), in addition to distractions, overcome thousands of difficulties and obstacles, to obtain the truth, repair into positive fruit The first author of the thesis is Li Wenwen, an assistant researcher, and Lu Wei, a postdoctoral researcher, and a researcher at The Institute of Immunology of Shanghai Jiaotong University, Professor Di Wen of Renji Hospital, Shanghai Jiaotong University, and Yang Caiming, a researcher at Shanghai Jiaotong University The study was also supported by Professor Cheng Jinke and Professor Su Bing of Shanghai Jiaotong University School of Medicine, Professor Fu Yangxin of UT Southwestern Medical Center, Professor Gobao Professor of Tongji University and Researcher Wang Yuxuan of the Institute of Biophysics of the Chinese Academy of Sciences (
Bio Valley Bioon.com
) Conference 2020 (Eleventh) International Symposium on Cell Therapy? __token .