Liang, Hua and Deng, Liufu and Hou, Yuzhu and Meng, Xiangjiao and Huang, Xiaona and Rao, Enyu and Zheng, Wenxin and Mauceri, Helena and Mack, Matthias and Xu, Meng and Fu, Yang-Xin and Weichselbaum, Ralph R. (2017) Host STING-dependent MDSC mobilization drives extrinsic radiation resistance. NATURE COMMUNICATIONS, 8: 1736. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Radiotherapy induces and promotes innate and adaptive immunity in which host STING plays an important role. However, radioresistance in irradiated tumors can also develop, resulting in relapse. Here we report a mechanism by which extrinsic resistance develops after local ablative radiation that relies on the immunosuppressive action of STING. The STING/type I interferon pathway enhances suppressive inflammation in tumors by recruiting myeloid cells in part via the CCR2 pathway. Germ-line knockouts of CCR2 or treatment with an anti-CCR2 antibody results in blockade of radiation-induced MDSC infiltration. Treatment with anti-CCR2 antibody alleviates immunosuppression following activation of the STING pathway, enhancing the anti-tumor effects of STING agonists and radiotherapy. We propose that radiation-induced STING activation is immunosuppressive due to (monocytic) M-MDSC infiltration, which results in tumor radioresistance. Furthermore, the immunosuppressive effects of radiotherapy and STING agonists can be abrogated in humans by a translational strategy involving anti-CCR2 antibody treatment to improve radiotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERSISTENT LCMV INFECTION; IMMUNOGENIC TUMORS; CELLS; CANCER; CCR2; INFLAMMATION; BLOCKADE; AUTOIMMUNITY; RADIOTHERAPY; RECOGNITION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 25 Feb 2019 14:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1830 |
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