Host STING-dependent MDSC mobilization drives extrinsic radiation resistance

Hua Liang, Liufu Deng (), Yuzhu Hou, Xiangjiao Meng, Xiaona Huang, Enyu Rao, Wenxin Zheng, Helena Mauceri, Matthias Mack, Meng Xu, Yang-Xin Fu () and Ralph R. Weichselbaum ()
Additional contact information
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
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

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01566-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01566-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01566-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().