[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-413314-105":59,"doc-detail-413314-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","cancer-systemically-inducing-trained-immunity-overcomes-solid-tumors-immunosuppressive-microenvironment","Cancer - Systemically inducing trained immunity overcomes solid tumors’ immunosuppressive microenvironment","","Hematopoietic bone marrow progenitors contribute to cancer-induced immunosuppression, and trained immunity induction can potentiate checkpoint blockade. This study investigates how systemic trained immunity induction reshapes the immunosuppressive tumor microenvironment. In a melanoma mouse model, tumor microenvironment changes paralleled functional shifts in hematopoiesis. Single-cell sequencing revealed a conversion of tumor-associated macrophages toward antitumor activity, while a combined trained immunity and checkpoint blockade therapy mobilized NK cells that activated T cells. Effectiveness was validated in mouse models of breast, lung, and pancreatic cancer.",{"@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/cancer-systemically-inducing-trained-immunity-overcomes-solid-tumors-immunosuppressive-microenvironment/413314/",{"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/cancer-systemically-inducing-trained-immunity-overcomes-solid-tumors-immunosuppressive-microenvironment/413314.png","ImageObject",300,407,{"name":92,"@type":93},"dhado","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",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},"What is the main problem addressed in the study?","Question",{"text":113,"@type":114},"The study targets cancer-induced immunosuppression driven by hematopoietic bone marrow progenitors and how it shapes an immunosuppressive tumor microenvironment.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does the study connect trained immunity to checkpoint blockade?",{"text":118,"@type":114},"It builds on prior findings that trained immunity induction using nanomedicine can potentiate checkpoint blockade, then tests how systemic induction can overcome the tumor microenvironment’s suppressive effects.",{"name":120,"@type":111,"acceptedAnswer":121},"What immune-cell changes were observed in the tumor and why do they matter?",{"text":122,"@type":114},"Single-cell sequencing showed a shift in tumor-associated macrophages from immunosuppressive to antitumorigenic states. The combination therapy also mobilized NK cells and, together with myeloid functional changes, effectively activated T cells.","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},413314,1790718968,{"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,"preview_page_count":4},5909893218464,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","CANCER  \nSystemically inducing trained immunity overcomes solid tumors’ immunosuppressive microenvironment  \nBram Priem1,2,3†, Lisa Willemsen4†, Tom Anbergen1,3, Yuri van Elsas1,3, Jeroen Deckers1,3, David P. Schrijver5, Stijn R.J. Hofstraat5, Iris V. Messing1, Jazz Munitz3, Dionne Honing1, Geoffrey Prévot3, Yohana C. Toner1, Judit Morla3, William Wang3, Anna Ranzenigo3,  \nIsabella Sirchia3, Tomas Post3,6, Raphaël Duivenvoorden3,6, Ewelina Kluza5, Glenn A.O. Cremers7, Joost H.C.M Kreijtz7, Carlos Pérez-Medina3,8, Mandy M.T. van Leent3,9, Abraham J.P. Teunissen3, Roy van der Meel5, Yi Zhou10, Chris Glass10, Jordi Ochando11, Leo A.B. Joosten12,13, Zahi A. Fayad3, RomanaT. Netea-Maier1, Mihai G. Netea1,14,15, Menno P.J. deWinther4, Thijs J. Beldman1,  \nArjan W. Griffioen2, Willem J.M. Mulder1,5*  \nHematopoietic bone marrow progenitors are increasingly implicated as an origin of immunosuppression in cancer. We have previously shown that trained immunity induction using nanomedicine potentiates checkpoint blockade therapy. Here, we studied how this approach’s induction of trained immunity systemically overcomes the immunosuppressive tumor microenvironment. We found changes in the tumor microenvironment to mirror functional changes in the hematopoietic system in a melanoma mouse model. Single cell sequencing methods disclosed a shift in the tumor-associated macrophage population from immunosuppressive to antitumorigenic. Uniquely, a trained immunity and checkpoint blockade combination therapy mobilized natural killer cells which, in conjunction with the functional changes in the myeloid cell compartment, effectively activated T cells. Last, we established the effectiveness of our approach in mouse models of breast, lung, and pancreatic cancer. Collectively, our data show that the systemic induction of trained immunity rebalances the immune system for effective checkpoint blockade therapy.  \ncopyright © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S.  \nGovernment Works. distributed under a creative commons Attribution noncommercial license 4.0 (cc BY-nc) .  \nINTRODUCTION  \nAccumulating evidence implicates bone marrow progenitor cells in cancer-induced immunosuppression. Preclinical and clinical studies suggest that—through the release of cytokines, chemokines, and metabolites—tumors can induce systemic immunosuppression already from the level of bone marrow hematopoietic stem and progenitor cells (1, 2) . The resulting progenitor cells’ tolerogenic state drives the formation of immune cells with an aberrant functional program and their accumulation in the tumor microenvironment. In line with this concept, Rabold et al. (3) showed that myeloid cells  \n1department of internal Medicine, Radboud University Medical center, nijmegen, netherlands. 2Angiogenesis laboratory, Amsterdam UMc, cancer center Amsterdam, Amsterdam, netherlands. 3Biomedical engineering and imaging institute, icahn School of Medicine at Mount Sinai, new York, nY, USA. 4department of Medical Biochemistry, Amsterdam cardiovascular Sciences, Atherosclerosis & ischemic Syndromes; Amsterdam institute for infection and immunity, inflammatory diseases,(Ai&ii), Amsterdam University Medical centers, location University of Amsterdam, Amsterdam, netherlands. 5laboratory of chemical Biology, department of Biochemical engineering, eindhoven University of technology, eindhoven, netherlands. 6department of nephrology, Radboud institute for Molecular life Sciences, Radboud University Medical center, nijmegen, netherlands. 7trained therapeutix discovery, 5349 AB Oss, netherlands. 8centro nacional de investigaciones cardiovasculares carlos iii, Madrid, Spain. 9cardiovascular Research institute, icahn School of Medicine at Mount Sinai, new York, nY, USA. 10department of cellular and Molecular Medicine, School of Medicine, University of california, San diego, la Jolla, cA, USA. 11department of Medic","cbCaiib93DaG2HFN","https://ap.wps.com/l/cbCaiib93DaG2HFN","pdf",9873327,16,"English","# Introduction\n## Bone marrow progenitors and systemic immunosuppression\n## Trained immunity and epigenetic reprogramming\n## Rationale for systemic trained immunity to counter tumors","[{\"question\":\"What is the main problem addressed in the study?\",\"answer\":\"The study targets cancer-induced immunosuppression driven by hematopoietic bone marrow progenitors and how it shapes an immunosuppressive tumor microenvironment.\"},{\"question\":\"How does the study connect trained immunity to checkpoint blockade?\",\"answer\":\"It builds on prior findings that trained immunity induction using nanomedicine can potentiate checkpoint blockade, then tests how systemic induction can overcome the tumor microenvironment’s suppressive effects.\"},{\"question\":\"What immune-cell changes were observed in the tumor and why do they matter?\",\"answer\":\"Single-cell sequencing showed a shift in tumor-associated macrophages from immunosuppressive to antitumorigenic states. The combination therapy also mobilized NK cells and, together with myeloid functional changes, effectively activated T cells.\"}]","Cancer - Systemically inducing trained immunity overcomes solid tumors’ immunosuppressive microenvironment | PDF",1790594431]