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IR can trigger immunogenic cell death (ICD), activating innate and adaptive immunity, but this immune activation is often transient and can be counteracted by wound-healing programs that promote immunosuppression. Multiple cellular and molecular mechanisms contribute to radioresistance. The paper summarizes IR-driven changes in the tumor immune landscape, detailing ICD and subsequent myeloid and lymphoid responses, to inform strategies for strengthening future cancer immunotherapies.",{"@graph":69,"@context":122},[70,84,105],{"@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/harnessing-the-immunological-effects-of-radiation-to-improve-immunotherapies-in-cancer-read-online-free/384643/",{"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/harnessing-the-immunological-effects-of-radiation-to-improve-immunotherapies-in-cancer-read-online-free/384643.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does ionizing radiation influence cancer treatment beyond direct DNA damage?","Question",{"text":112,"@type":113},"Ionizing radiation can induce immunogenic cell death that activates innate and adaptive immunity against cancer.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why can IR effectiveness be limited even when immune activation occurs?",{"text":117,"@type":113},"The immune response is often transient, while wound-healing processes and recruited immunosuppressive cell types can dampen early antitumor efforts and contribute to radioresistance.",{"name":119,"@type":110,"acceptedAnswer":120},"What immune responses are discussed after IR exposure?",{"text":121,"@type":113},"The document discusses immunogenic cell death as well as dynamic myeloid and lymphoid responses that reshape the immune landscape within tumors.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},384643,1790790466,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","Review  \nHarnessing the Immunological Effects of Radiation to Improve Immunotherapies in Cancer  \nGary Hannon 1,2,3, Maggie L. Lesch 1,2,3,4 and Scott A. Gerber 1,2,3,4, *  \nCitation: Hannon, G.; Lesch, M.L.; Gerber, S.A. Harnessing the Immunological Effects of Radiation to Improve Immunotherapies in Cancer. Int. J. Mol. Sci. 2023, 24, 7359 .  \n[https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24087359  \nAcademic Editor: Emily Capone  \nReceived: 22 March 2023  \nRevised: 12 April 2023  \nAccepted: 13 April 2023  \nPublished: 16 April 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA; [gary_hannon@urmc.rochester.edu](gary_hannon@urmc.rochester.edu) (G.H.); [maggie_lesch@urmc.rochester.edu](maggie_lesch@urmc.rochester.edu) (M.L.L.)  \n2 Center for Tumor Immunology Research, University of Rochester Medical Center, Rochester, NY 14642, USA  \n3 Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA  \n4 Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA  \n* Correspondence: [scott_gerber@urmc.rochester.edu](scott_gerber@urmc.rochester.edu)  \nAbstract: Ionizing radiation (IR) is used to treat 50% of cancers. While the cytotoxic effects related to DNA damage with IR have been known since the early 20th century, the role of the immune system in the treatment response is still yet to be fully determined. IR can induce immunogenic cell death (ICD), which activates innate and adaptive immunity against the cancer. It has also been widely reported that an intact immune system is essential to IR efficacy. However, this response is typically transient, and wound healing processes also become upregulated, dampening early immunological efforts to overcome the disease. This immune suppression involves many complex cellular and molecular mechanisms that ultimately result in the generation of radioresistance in many cases. Understanding the mechanisms behind these responses is challenging as the effects are extensive and often occur simultaneously within the tumor. Here, we describe the effects of IR on the immune landscape of tumors. ICD, along with myeloid and lymphoid responses to IR, are discussed, with the hope of shedding light on the complex immune stimulatory and immunosuppressive responses involved with this cornerstone cancer treatment. Leveraging these immunological effects can provide a platform for improving immunotherapy efficacy in the future.  \nKeywords: radiation; cancer; immunity; immunotherapies; immunogenic cell death  \n1. Introduction  \nIonizing radiation (IR) is a prevalent non-surgical intervention for achieving cures in cancer [1] . Approximately 50% of cancers are treated with some form of IR [2,3], and it is estimated that this contributes to 40% of cures [4,5] . While the cytotoxic effects of IR on cancer were first appreciated in the early 20th century, following Röntgen's discovery of X-rays in 1895 [6], the complex mechanisms by which the tumor microenvironment (TME) is altered following IR are still being elucidated today [7–9] .  \nNotably, the immune modulatory potential of IR has gained particular interest. Cancers exploit naturally occurring immunosuppressive mechanisms to facilitate their growth and metastasis, and many reports show that IR is capable of reprogramming the TME to alleviate this suppression and even achieve abscopal effects in rare cases [10] . Following IR exposure, cancer cells undergo an immunogenic form of cell death which results in antigen presenting cell (APC) activation and ","cbCaimLYGzYvbhDD","https://ap.wps.com/l/cbCaimLYGzYvbhDD","pdf",2603853,18,"English","# Introduction\n# Immunogenic Cell Death","[{\"question\":\"How does ionizing radiation influence cancer treatment beyond direct DNA damage?\",\"answer\":\"Ionizing radiation can induce immunogenic cell death that activates innate and adaptive immunity against cancer.\"},{\"question\":\"Why can IR effectiveness be limited even when immune activation occurs?\",\"answer\":\"The immune response is often transient, while wound-healing processes and recruited immunosuppressive cell types can dampen early antitumor efforts and contribute to radioresistance.\"},{\"question\":\"What immune responses are discussed after IR exposure?\",\"answer\":\"The document discusses immunogenic cell death as well as dynamic myeloid and lymphoid responses that reshape the immune landscape within tumors.\"}]","Harnessing the Immunological Effects of Radiation to Improve Immunotherapies in Cancer - read online free | PDF",1790264337,45]