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• W3101474684 startingPage "108620" @default.
• W3101474684 abstract "Lung cancer remains the leading cause of cancer-related deaths and despite extensive research, the survival rate of lung cancer patients remains significantly low. Recent data reveal that aberrant Kras signaling drives regulatory T cells (Tregs) present in lung tumor microenvironment to establish immune deregulation and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras in Treg-related immunosuppression and its involvement in tumor-associated metabolic reprogramming. Findings reveal Tregs to prompt GATA3/NOS2-related immunosuppression via STING inhibition which triggers a decline in CD4+ T infiltration, and a subsequent increase in lung metastatic burden. Enhanced Treg expression was also associated with low T/MDSC ratio through restriction of CD8+CD44+CD62L− T effector cells, contributing to a tumor-promoting status. Specifically, TIM3+/LAG3+ Tregs prompted Kras-related immunosuppressive chemoresistance and were associated with T cell dysfunction. This Treg-dependent immunosuppression correlated with CD8 T cell exhaustion phenotype and ILC2 augmentation in mice. Moreover, enhanced Treg expression promoted activation-induced cell death (AICD) of T lymphocytes and guided lymph node metastasis in vivo. Overall, these findings demonstrate the multifaceted roles of Tregs in sustaining lung immunosuppressive neoplasia through tumor microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors." @default.
• W3101474684 created "2020-11-23" @default.
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• W3101474684 date "2021-01-01" @default.
• W3101474684 modified "2023-10-17" @default.
• W3101474684 title "Treg-dependent immunosuppression triggers effector T cell dysfunction via the STING/ILC2 axis" @default.
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• W3101474684 doi "https://doi.org/10.1016/j.clim.2020.108620" @default.
• W3101474684 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33176208" @default.
• W3101474684 hasPublicationYear "2021" @default.
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