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This review analyzes RT–immune system interactions, detailing varied effects across immune cell populations and outlining emerging approaches to improve outcomes. It covers renewed low-dose irradiation for non-malignant disorders, RT for graft-versus-host disease management, and fractionation-dependent immune modulation. The review discusses abscopal effects, the role of tumor-draining lymph nodes, and innovations such as FLASH RT and immune-preserving targeted strategies, emphasizing personalization, biomarkers, and optimized combinations.",{"@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/radiotherapy-and-immune-system-interactions-historical-perspectives-and-clinical-advancements/352929/",{"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/radiotherapy-and-immune-system-interactions-historical-perspectives-and-clinical-advancements/352929.png","ImageObject",300,407,{"name":92,"@type":93},"Đào","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does radiotherapy influence the immune system according to the review?","Question",{"text":113,"@type":114},"The review describes complex, cell-specific effects of RT on multiple immune cell populations and highlights systemic immune responses mediated through interactions with key immune pathways and lymphatic structures.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is the abscopal effect and why is it clinically important here?",{"text":118,"@type":114},"The abscopal effect refers to effects occurring outside the irradiated field, indicating systemic immune activation. The review addresses its clinical implications and notes that its existence remains debated.",{"name":120,"@type":111,"acceptedAnswer":121},"Why are fractionation and tumor-draining lymph nodes emphasized in optimizing outcomes?",{"text":122,"@type":114},"Fractionation is presented as a major lever for modulating immune responses, while tumor-draining lymph nodes are highlighted as central mediators of systemic immune activity, both contributing to improved therapeutic potential while limiting adverse effects.","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},352929,1790186642,{"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":36},1374402968488,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Molecular Carcinogenesis   \nREVIEW ARTICLE   \nRadiotherapy and Immune System Interactions Historical Perspectives and Clinical Advancements  \nSafiy Yahia1 | Ayman J. Oweida2 | Houda Bahig3 | Daniel Taussky3   \n1Campus de Rimouski, Université Laval, Quebec City, Canada | 2Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Canada | 3Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada  \nCorrespondence: Daniel Taussky ([daniel.taussky.chum@ssss.gouv.qc.ca](daniel.taussky.chum@ssss.gouv.qc.ca))  \nReceived: 2 April 2025 | Revised: 27 October 2025 | Accepted: 13 January 2026  \nKeywords: fractionation | immune system | low‐dose irradiation | lymphatic system | radiotherapy  \nABSTRACT  \nRadiotherapy (RT) has evolved significantly since its inception from treating benign conditions to becoming a cornerstone of cancer treatment. This review examines the complex interactions between RT and the immune system, highlighting its diverse effects on various immune cell populations, and exploring emerging strategies to enhance therapeutic outcomes. We discuss lessons learned from the re‐emergence of low‐dose irradiation for non‐malignant disorders, the use of RT in managing graft‐ versus‐host disease, and the importance of fractionation in modulating immune responses. This review addresses abscopal effects and their clinical implications. We emphasize the critical role of tumor‐draining lymph nodes in mediating systemic immune responses. Recent advancements, including FLASH radiotherapy and targeted approaches to preserving immune function, have been explored. By integrating historical insights with contemporary research, this review aims to guide future RT practices and optimize their immunomodulatory potential, while minimizing adverse effects. We conclude by emphasizing the need for personalized approaches, biomarker identification, and innovative combination therapies to maximize the efficacy of RT in oncology.  \n1 | Introduction  \nRadiotherapy (RT) has a significant history, originating from Wilhelm Röntgen's discovery of X‐rays in 1895, and Henri Becquerel's discovery of nuclear radiation in 1896. By the early 20th century, the potential of using X‐rays and radioactivity as therapeutic agents had become apparent. Well‐known is that during the 1920s, the idea emerged that radium could act as a general stimulant, leading to the consumption of radium“elixirs.” Radithor, for example, contained radioactive radium and was marketed as a general stimulant against fatigue and impotence. However, initially, X‐rays were mainly used to treat superficial inflammation because of the difficulty in penetrating deeper regions of the body [1] . However, in 1903, Soddy suggested that people with tuberculosis, the most dreaded disease at the time, might benefit from inhaling radioactive gas [2] . RT application to immune‐related diseases, such as asthma and  \narthritis, had demonstrated its immune‐modulating potential. The effect on leukocytes was also observed by Ewing at the beginning of the 20th century [3] . On the other hand, adverse effects soon became apparent with reports of severe radiation effects and related deaths. Early observations noted a biphasic dose‐response phenomenon to RT, called hormesis [4], where high doses cause tissue damage, whereas low doses have protective effects.  \nUnderstanding the complex interactions between RT and the immune system can guide future strategies to enhance therapeutic outcomes, while minimizing adverse effects. In this review, we aim to show avenues for refining RT practices and maximizing their potential. The combination of RT with immunotherapy can potentially increase its effectiveness [5] . However, the interactions between them showed conflicting results. We explore these interactions and propose better  \nThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits u","cbCailtRMiUn31Nh","https://ap.wps.com/l/cbCailtRMiUn31Nh","pdf",1846426,16,"English","# Introduction\n## Historical Review of the Interaction Between RT and the Immune System","[{\"question\":\"How does radiotherapy influence the immune system according to the review?\",\"answer\":\"The review describes complex, cell-specific effects of RT on multiple immune cell populations and highlights systemic immune responses mediated through interactions with key immune pathways and lymphatic structures.\"},{\"question\":\"What is the abscopal effect and why is it clinically important here?\",\"answer\":\"The abscopal effect refers to effects occurring outside the irradiated field, indicating systemic immune activation. The review addresses its clinical implications and notes that its existence remains debated.\"},{\"question\":\"Why are fractionation and tumor-draining lymph nodes emphasized in optimizing outcomes?\",\"answer\":\"Fractionation is presented as a major lever for modulating immune responses, while tumor-draining lymph nodes are highlighted as central mediators of systemic immune activity, both contributing to improved therapeutic potential while limiting adverse effects.\"}]","Radiotherapy and Immune System Interactions - Historical Perspectives and Clinical Advancements | PDF",1790102018]