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RT can promote tumor-associated macrophage and myeloid-derived suppressor cell (MDSC) activity, enabling MDSCs to blunt antitumor immunity and support therapeutic resistance. RT-triggered vascular damage and TME hypoxia alter cytokine and chemokine signaling, recruiting MDSCs via CCR2. cGAS-STING activation, HIF-1, and VEGF mobilize MDSCs, which suppress immune surveillance through ROS, nitric oxide, arginase-1, and reduced T-cell receptor reactivity.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/radiation-therapy-and-myeloid-derived-suppressor-cells-breaking-down-their-cancerous-partnership/377488/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/radiation-therapy-and-myeloid-derived-suppressor-cells-breaking-down-their-cancerous-partnership/377488.png","ImageObject",300,407,{"name":92,"@type":93},"kopisore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does radiation therapy contribute to immunosuppression in the tumor microenvironment?","Question",{"text":113,"@type":114},"Radiation can shift immune activity toward suppression by promoting the accumulation and activation of myeloid-derived suppressor cells (MDSCs), alongside tumor-associated macrophages. This alters cytokine and chemokine signaling and supports therapeutic resistance.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What mechanisms recruit MDSCs after radiation therapy?",{"text":118,"@type":114},"RT-induced vascular damage triggers inflammatory signaling and hypoxia, while RT also modifies cytokine/chemokine signaling to enhance MDSC accumulation. The cGAS-STING pathway can recruit MDSCs through a CCR2-mediated mechanism.",{"name":120,"@type":111,"acceptedAnswer":121},"How do MDSCs suppress antitumor immune responses following recruitment?",{"text":122,"@type":114},"MDSCs inhibit immune surveillance by releasing reactive oxygen species and increasing nitric oxide production via inducible nitric oxide synthase. They also overexpress arginase-1, degrading L-arginine and downregulating CD3z to reduce T-cell receptor reactivity.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},377488,1790526355,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},962090880963,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Int J Radiat Oncol Biol Phys. Author manuscript; available in PMC 2024 May 10. |\n| --- | --- |\n\nPublished in final edited form as:  \nInt J Radiat Oncol Biol Phys. 2024 May 01; 119(1): 42–55. doi:10.1016/j.ijrobp.2023.11.050 .  \nRadiation Therapy and Myeloid-Derived Suppressor Cells: Breaking Down Their Cancerous Partnership  \nKyra M. Boorsma Bergerud* , Matthew Berkseth, PhD†, Drew M. Pardoll, MD, PhD‡, Sudipto Ganguly, PhD‡, Lawrence R. Kleinberg, MD§ , Jessica Lawrence, DVM, DACVIM (Onc), DACVR (Rad Onc), DECVDI (add on Rad Onc)‖, David J. Odde, PhD¶ , David A. Largaespada, PhD\\# , Stephanie A. Terezakis, MD†, Lindsey Sloan, MD, PhD†  \n*College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota †Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota ‡Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland  \n§ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland  \n‖ Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, Minnesota ¶Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota  \n\\# Departments of Pediatrics and Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota  \nAbstract  \nRadiation therapy (RT) has been a primary treatment modality in cancer for decades. Increasing evidence suggests that RT can induce an immunosuppressive shift via upregulation of cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) . MDSCs inhibit antitumor immunity through potent immunosuppressive mechanisms and have the potential to be crucial tools for cancer prognosis and treatment. MDSCs interact with many different pathways, desensitizing tumor tissue and interacting with tumor cells to promote therapeutic resistance. Vascular damage induced by RT triggers an inflammatory signaling cascade and potentiates hypoxia in the tumor microenvironment (TME). RT can also drastically modify cytokine and chemokine signaling in the TME to promote the accumulation of MDSCs. RT activation of the cGAS-STING cytosolic DNA sensing pathway recruits MDSCs through a CCR2-mediated mechanism, inhibiting the production of type 1 interferons and hampering  \nThis is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/))  \nCorresponding author: Lindsey Sloan, MD, PhD; [sloan153@umn.edu](sloan153@umn.edu).  \nDisclosures: L.R.K. has contracts or grants with Bristol Myers Squibb, Novartis, Novocure, and Incyte. L.S. acknowledges funding from the Department of Radiation Oncology, Masonic Cancer Center, and the Medical School at the University of Minnesota and from the National Institutes of Health under grant numbers P01 CA254849 and U54 CA268069 . D.J.O. acknowledges funding from the National Institutes of Health under grant numbers U54 CA210190, P01 CA254849, and U54 CA268069 . Geezer R. Nelson supported an undergraduate student summer internship within the Sloan Laboratory at the University of Minnesota. The medical artwork in this publication was funded by startup funding to the Sloan Laboratory at the University of Minnesota Medical School, Minneapolis, MN. Data Sharing Statement: Research data are stored in an institutional repository and will be shared upon request to the corresponding author.  \nAuthor Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \nBoorsma Bergerud et al. Page 2  \nantitumor activity and immune surveillance in the TME. The upregulation of hypoxia-inducible factor-1 and vascular endothelial growth factor mobilizes MDSCs to the TME. After recruitment, MDSCs promote immunosuppression by releasing reactive oxygen specie","cbCaimaqEnY5HOUE","https://ap.wps.com/l/cbCaimaqEnY5HOUE","pdf",1215527,23,"English","# Abstract\n## Radiation therapy and systemic immunity\n## Lymphopenia and outcomes","[{\"question\":\"How does radiation therapy contribute to immunosuppression in the tumor microenvironment?\",\"answer\":\"Radiation can shift immune activity toward suppression by promoting the accumulation and activation of myeloid-derived suppressor cells (MDSCs), alongside tumor-associated macrophages. This alters cytokine and chemokine signaling and supports therapeutic resistance.\"},{\"question\":\"What mechanisms recruit MDSCs after radiation therapy?\",\"answer\":\"RT-induced vascular damage triggers inflammatory signaling and hypoxia, while RT also modifies cytokine/chemokine signaling to enhance MDSC accumulation. The cGAS-STING pathway can recruit MDSCs through a CCR2-mediated mechanism.\"},{\"question\":\"How do MDSCs suppress antitumor immune responses following recruitment?\",\"answer\":\"MDSCs inhibit immune surveillance by releasing reactive oxygen species and increasing nitric oxide production via inducible nitric oxide synthase. They also overexpress arginase-1, degrading L-arginine and downregulating CD3z to reduce T-cell receptor reactivity.\"}]","Radiation Therapy and Myeloid-Derived Suppressor Cells - Breaking Down Their Cancerous Partnership | PDF",1790225641,58]