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. 2021 Dec 15;12:812210. doi: 10.3389/fimmu.2021.812210

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Copyright © 2021 He, Barsoumian, Bertolet, Verma, Leuschner, Koay, Ludmir, Hsu, Pisipati, Voss, Puebla-Osorio, Cortez and Welsh

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Reprogramming the tumor stroma by LDRT in liver metastases. (Left) The efficacy of immunotherapy is limited by unfavorable conditions in liver metastatic tumors such as a dense stroma, a low ratio of M1-to-M2 macrophages, increased TGF-β, vascular endothelial growth factor (VEGF) and cancer associated fibroblasts (CAFs). Liver resident cells, Kupffer cells, monocytic myeloid-derived suppressor cells (mMDSCs), and hepatic stellate cells (HSCs) promote Treg expansion through IL-10 and TGF-β release. (Right) Effect of low-dose radiotherapy (LDRT) on the immunosuppressive tumor microenvironment. LDRT repolarizes macrophages, decreases CAFs, and reduces TGF-β and VEGF. T cells and NK cells infiltrate the tumor through the disrupted stroma and receive positive stimulation from M1 macrophages.