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Activation of STING inhibits cervical cancer tumor growth through enhancing the anti-tumor immune response

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Abstract

Cervical cancer remains the second leading cause of gynecologic cancer-related mortality among women worldwide. STING (stimulator of interferon genes) was reported to be involved in the immune surveillance of tumors. However, the specific role of STING in cervical cancer remains unclear. In this study, we found that the cGAS (Cyclic GMP-AMP synthase)/STING signal decreased in cervical cancer cells. Knockdown of STING by siRNA enhanced the cell viability and migration of cervical cancer cells, while activation of STING by ADU-S100 inhibited the cell viability of cervical cancer cells, with no effect on the migration and apoptosis. In addition, ADU-S100 promoted the secretion of IFNβ and IL-6, and the activation of TBK1 (TANK-binding kinase 1)/NF-κB (nuclear factor kappa-B) pathway. Meanwhile, knockdown of STING inhibited the production of IFNβ and IL-6 that were triggered by dsDNA and suppressed the TBK1/NF-κB signaling. ADU-S100 also suppressed tumor growth in vivo and increased the tumor-infiltrating CD8+ T cell and CD103+ dendritic cell numbers. The NF-κB signal inhibitor limited the increasing numbers of CD8+ T cell and CD103+ dendritic cells induced by ADU-S100, without influence on tumor growth. Hence, our study suggested that STING could serve as a potential novel immunotherapeutic target for cervical cancer.

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  1. Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No.277 West yanta road, Xi’an, 710061, China

    Fan Shi, Jin Su, Juan Wang, Zi Liu & Tao Wang

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  1. Fan Shi
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Shi, F., Su, J., Wang, J. et al. Activation of STING inhibits cervical cancer tumor growth through enhancing the anti-tumor immune response. Mol Cell Biochem 476, 1015–1024 (2021). https://doi.org/10.1007/s11010-020-03967-5

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