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Metastatic lesion TIME is shaped by the organ’s underlying immune contexture, and metastatic site strongly influences prognosis after ICI therapy. Liver metastases show reduced ICI responsiveness, likely reflecting differences in metastatic TIME. Combining radiotherapy (RT) with ICIs is a strategy to counter resistance, since RT can trigger local and systemic immune activation, potentially enhancing ICI responses. This review evaluates how TIME varies by metastatic location and how RT-induced TIME modulation could optimize RT-ICI outcomes.",{"@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/implications-of-the-organ-specific-immune-environment-for-immune-priming-effect-of-radiotherapy-in-metastatic-setting/383511/",{"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/implications-of-the-organ-specific-immune-environment-for-immune-priming-effect-of-radiotherapy-in-metastatic-setting/383511.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does metastatic location influence outcomes after immune checkpoint inhibitor therapy?","Question",{"text":112,"@type":113},"Metastatic site is linked to prognosis because the tumour immune microenvironment (TIME) differs by the organ’s immune contexture. Variations in metastatic TIME can explain response heterogeneity across organs.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why do patients with liver metastases often respond less to ICIs?",{"text":117,"@type":113},"Liver metastases are less likely to respond, likely due to differences in the metastatic TIME. The underlying liver immune context can reduce the effectiveness of ICIs compared with other organs.",{"name":119,"@type":110,"acceptedAnswer":120},"What role can radiotherapy play when combined with immune checkpoint inhibitors?",{"text":121,"@type":113},"Radiotherapy can induce local and systemic immune reactions that promote immune priming and potentially improve responses to ICIs. The review also discusses how RT-induced changes in TIME and the systemic immune system may enhance RT-ICI combinations.","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},383511,1790293673,{"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":39,"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},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","biomolecules  \nReview  \nImplications of the Organ-Specific Immune Environment for Immune Priming Effect of Radiotherapy in Metastatic Setting  \nJulien Pierrard 1,2, *, Genevi±ve Van Ooteghem 1,2 and Marc Van den Eynde 1,3  \nCitation: Pierrard, J.; Van Ooteghem, G.; Van den Eynde, M. Implications of the Organ-Specific Immune Environment for Immune Priming Effect of Radiotherapy in Metastatic Setting. Biomolecules 2023, 13, 689. [https://](https://)[ ](https://)[doi.org/10.3390/biom13040689](doi.org/10.3390/biom13040689)  \nAcademic Editor: Peixin Dong  \nReceived: 21 February 2023  \nRevised: 7 April 2023  \nAccepted: 17 April 2023  \nPublished: 18 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 UCLouvain, Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institute de Recherche Experimentale et Clinique (IREC), 1200 Brussels, Belgium  \n2 Radiation Oncology Department, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium  \n3 Medical Oncology Department, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium  \n* [Correspondence: julien.pierrard@saintluc.uclouvain.be](Correspondence: julien.pierrard@saintluc.uclouvain.be)  \nAbstract: With the development of immune checkpoint inhibitors (ICIs), the tumour immune microenvironment (TIME) has been increasingly considered to improve cancer management. The TIME of metastatic lesions is strongly influenced by the underlying immune contexture of the organ in which they are located. The metastatic location itself appears to be an important prognostic factor in predicting outcomes after ICI treatment in cancer patients. Patients with liver metastases are less likely to respond to ICIs than patients with metastases in other organs, likely due to variations in the metastatic TIME. Combining additional treatment modalities is an option to overcome this resistance. Radiotherapy (RT) and ICIs have been investigated together as an option to treat various metastatic cancers. RT can induce a local and systemic immune reaction, which can promote the patient's response to ICIs. Here, we review the differential impact of the TIME according to metastatic location. We also explore how RT-induced TIME modifications could be modulated to improve outcomes of RT-ICI combinations.  \nKeywords: tumour immune microenvironment; radio-immunotherapy combination; liver metastases; liver immune system  \n1. Introduction  \nDue to recent advances in the understanding of cancer, tumoral cells are no longer considered the only target for treatment. The tumour microenvironment also plays an important role in the disease process and response to treatment. A growing body of evidence highlights the significant role of tumour-infiltrating immune cells, which are directly involved in immune destruction evasion, a new cancer hallmark [1] . Targeting immune evasion has led to one of the most significant advances in cancer treatment, namely immunotherapy. The prognosis for both locally advanced and metastatic tumours is significantly improved by inhibiting immunological checkpoints that suppress antitumoral immune responses, such as programmed cell death (PD-1), its ligand PD-L1, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) . However, the effects of immune checkpoint inhibitor (ICI) immunotherapy differ considerably across tumour histology. Excellent outcomes have been demonstrated for non-small cell lung cancer (NSCLC), melanoma, and colorectal cancer (CRC) with high microsatellite instability (MSI)/deficiency in mismatch repair (dMMR) mechanisms. However, results for other primary cancers, such as prostate cancer, hormone-sensitive breast cancer, and CRC with microsatellite stability (MS","cbCairqT4qkK9ohD","https://ap.wps.com/l/cbCairqT4qkK9ohD","pdf",2654738,18,"English","# Abstract\n## Introduction\n## Metastatic Location Matters\n### Liver Metastases","[{\"question\":\"How does metastatic location influence outcomes after immune checkpoint inhibitor therapy?\",\"answer\":\"Metastatic site is linked to prognosis because the tumour immune microenvironment (TIME) differs by the organ’s immune contexture. Variations in metastatic TIME can explain response heterogeneity across organs.\"},{\"question\":\"Why do patients with liver metastases often respond less to ICIs?\",\"answer\":\"Liver metastases are less likely to respond, likely due to differences in the metastatic TIME. The underlying liver immune context can reduce the effectiveness of ICIs compared with other organs.\"},{\"question\":\"What role can radiotherapy play when combined with immune checkpoint inhibitors?\",\"answer\":\"Radiotherapy can induce local and systemic immune reactions that promote immune priming and potentially improve responses to ICIs. The review also discusses how RT-induced changes in TIME and the systemic immune system may enhance RT-ICI combinations.\"}]","Implications of the Organ-Specific Immune Environment for Immune Priming Effect of Radiotherapy in Metastatic Setting | PDF",1790257424,45]