Author
Listed:
- Hua Liang
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
- Liufu Deng
(Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South)
- Yuzhu Hou
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
- Xiangjiao Meng
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago
Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science)
- Xiaona Huang
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
- Enyu Rao
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
- Wenxin Zheng
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
- Helena Mauceri
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
- Matthias Mack
(University of Regensburg)
- Meng Xu
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
- Yang-Xin Fu
(University of Texas Southwestern Medical Center)
- Ralph R. Weichselbaum
(Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago)
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.
Suggested Citation
Hua Liang & Liufu Deng & Yuzhu Hou & Xiangjiao Meng & Xiaona Huang & Enyu Rao & Wenxin Zheng & Helena Mauceri & Matthias Mack & Meng Xu & Yang-Xin Fu & Ralph R. Weichselbaum, 2017.
"Host STING-dependent MDSC mobilization drives extrinsic radiation resistance,"
Nature Communications, Nature, vol. 8(1), pages 1-10, December.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01566-5
DOI: 10.1038/s41467-017-01566-5
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01566-5. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.