[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332114-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332114-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","targeting-the-innate-immune-system-in-pediatric-and-adult-aml","Targeting the innate immune system in pediatric and adult AML","","T cell-based immunotherapies have improved outcomes across many cancers, but progress for both adult and pediatric acute myeloid leukemia (AML) has been slower, hindered by limited target antigens and insufficient understanding of the immunosuppressive tumor microenvironment. AML studies have mainly characterized T cells, while innate lineages such as monocytes, granulocytes, and NK cells are less explored. Innate immune plasticity and functional impairment may drive immunosuppression, so detailed innate immune compartment profiling is urgently needed. This review consolidates current knowledge on innate immunity in AML and discusses how targeting its components could strengthen T cell-based and other immunotherapeutic strategies.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/targeting-the-innate-immune-system-in-pediatric-and-adult-aml/332114/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/targeting-the-innate-immune-system-in-pediatric-and-adult-aml/332114.png","ImageObject",300,407,{"name":42,"@type":43},"Ivy","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",13,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why has immunotherapy progress been slower for adult and pediatric AML compared with other cancers?","Question",{"text":63,"@type":64},"Development has been limited by the need to identify suitable target antigens and by an incomplete understanding of the immunosuppressive tumor microenvironment. Clinical translation is further challenged by factors such as heterogeneity and limited effective targets.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What does the review say about the focus of earlier AML immune studies?",{"text":68,"@type":64},"Most immune characterization studies in AML have focused on T cells. Innate immune lineages such as monocytes, granulocytes, and NK cells have received less attention.",{"name":70,"@type":61,"acceptedAnswer":71},"How might innate immune cells affect immunotherapy outcomes in AML?",{"text":72,"@type":64},"Innate cells can contribute to an immunosuppressive tumor microenvironment and may underlie immunotherapy failure in hematological and solid malignancies. The review highlights roles of tumor-associated macrophages, neutrophils, and myeloid-derived suppressor cells, suggesting that targeting them could improve immunotherapeutic effectiveness.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332114,1790059386,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","Leukemia [www.nature.com/leu](www.nature.com/leu)  \nREVIEW ARTICLE OPEN   \nIMMUNOTHERAPY  \nTargeting the innate immune system in pediatric and adult AML  \nAlicia Perzolli 1,2, Joost B. Koedijk 1,2, C. Michel Zwaan 1,2,4 and Olaf Heidenreich 1,3,4 ✉  \n© The Author(s) 2024  \n|  |  |  |\n| --- | --- | --- |\n|  | While the introduction of T cell-based immunotherapies has improved outcomes in many cancer types, the development of immunotherapies for both adult and pediatric AML has been relatively slow and limited. In addition to the need to identify suitable target antigens, a better understanding of the immunosuppressive tumor microenvironment is necessary for the design of novel immunotherapy approaches. To date, most immune characterization studies in AML have focused on T cells, while innate immune lineages such as monocytes, granulocytes and natural killer (NK) cells, received less attention. In solid cancers, studies have shown that innate immune cells, such as macrophages, myeloid-derived suppressor cells and neutrophils are highly plastic and may differentiate into immunosuppressive cells depending on signals received in their microenvironment, while NK cells appear to be functionally impaired. Hence, an in-depth characterization of the innate immune compartment in the TME is urgently needed to guide the development of immunotherapeutic interventions for AML. In this review, we summarize the current knowledge on the innate immune compartment in AML, and we discuss how targeting its components may enhance T cell-based- and other |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| immunotherapeutic approaches. |  |  |\n|  | Leukemia (2024) 38:1191–1201; [https://doi.org/10.1038/s41375-024-02217-7](https://doi.org/10.1038/s41375-024-02217-7) |  |\n|  |  |  |\n\nINTRODUCTION  \nAcute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by uncontrolled clonal proliferation of myeloid progenitor cells in the bone marrow [1, 2] . Although survival has improved considerably over the past decades, about 70% of adult AML and 20–30% of pediatric AML patients in high income countries do not survive due to treatment-related toxicity and disease relapse [1–3] . Moreover, survivors often suffer from serious treatment-related side effects and long-term impaired quality of life [2] . Hence, targeted therapies are urgently needed to improve outcomes and to reduce treatment-related toxicity.  \nThe success of several traditional AML therapies such as allogeneic hematopoietic stem cell transplantation (allo-HSCT) and donor lymphocyte infusion relies on the ability of T and NK cells to recognize and eliminate leukemic cells, and illustrates the sensitivity of AML to functional immune cell cytotoxicity [4–6] . Although these observations support the use of immunotherapy for the treatment of AML, these traditional therapies are often accompanied by major side effects such as graft-versus-host disease, severe infections, organ toxicity and infertility [7, 8] . Interestingly, innovative T cell-based immunotherapies such as bispecific antibodies and chimeric antigen receptor (CAR) T cells hold the promise of immune-mediated tumor eradication with fewer side effects, as shown in the treatment of B-cell precursor  \nALL (BCP-ALL) with blinatumomab and CAR T cells [9] . Unfortunately, clinical trials of T cell-based immunotherapies in adult AML have shown disappointing efficacy, while trials for pediatric AML have only recently been initiated (e.g., NCT03825367) [3, 10, 11] . The challenges in translating the successes of these novel immunotherapies to AML may be explained by several factors, including genetic and clonal heterogeneity, paucity of suitable leukemic targets and the immunosuppressive tumor microenvironment (TME) . For AML, the alleged TME is the bone marrow (BM) and includes, next to tumor cells, immune and other normal hematopoietic, stromal, and endothelial cells [","cbCaio3pk7OVDHS7","https://ap.wps.com/l/cbCaio3pk7OVDHS7","pdf",1430431,11,"English","# Introduction\n# Innate immune compartment in AML\n## Role of innate cells in immunosuppressive microenvironment\n## Implications for immunotherapy design","[{\"question\":\"Why has immunotherapy progress been slower for adult and pediatric AML compared with other cancers?\",\"answer\":\"Development has been limited by the need to identify suitable target antigens and by an incomplete understanding of the immunosuppressive tumor microenvironment. Clinical translation is further challenged by factors such as heterogeneity and limited effective targets.\"},{\"question\":\"What does the review say about the focus of earlier AML immune studies?\",\"answer\":\"Most immune characterization studies in AML have focused on T cells. Innate immune lineages such as monocytes, granulocytes, and NK cells have received less attention.\"},{\"question\":\"How might innate immune cells affect immunotherapy outcomes in AML?\",\"answer\":\"Innate cells can contribute to an immunosuppressive tumor microenvironment and may underlie immunotherapy failure in hematological and solid malignancies. The review highlights roles of tumor-associated macrophages, neutrophils, and myeloid-derived suppressor cells, suggesting that targeting them could improve immunotherapeutic effectiveness.\"}]","Targeting the innate immune system in pediatric and adult AML | PDF",1789996840,28]