First Author | Liang H | Year | 2017 |
Journal | Nat Commun | Volume | 8 |
Issue | 1 | Pages | 1736 |
PubMed ID | 29170400 | Mgi Jnum | J:255925 |
Mgi Id | MGI:6106319 | Doi | 10.1038/s41467-017-01566-5 |
Citation | Liang H, et al. (2017) Host STING-dependent MDSC mobilization drives extrinsic radiation resistance. Nat Commun 8(1):1736 |
abstractText | 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. |