[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330342-105":59,"doc-detail-330342-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","pediatric-solid-cancers-issuearticle-review","Pediatric Solid Cancers - Issue/Article - Review","","Pediatric cancers remain a leading cause of death in childhood despite progress in diagnosis and treatment. While immunotherapies and other targeted approaches have improved outcomes in adults, results in pediatric cohorts are limited, largely due to pediatric tumor biology such as extreme heterogeneity and generally low tumor mutational burden. Limited efficacy is strongly linked to the tumor microenvironment (TME), characterized by scarce T-cell infiltration and abundant stromal cells that suppress lymphocytes and promote tumor growth. Progress in pediatric solid tumor therapy will therefore depend on modifying the TME while delivering more effective therapeutic agents; this review summarizes TME composition and recent advances in modulating immune cells within it.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/pediatric-solid-cancers-issuearticle-review/330342/",{"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/pediatric-solid-cancers-issuearticle-review/330342.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-26","2026-09-21",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},"Why do pediatric immunotherapy results lag behind adult outcomes?","Question",{"text":112,"@type":113},"Pediatric cohorts show disappointing results mainly due to tumor biological differences, including extreme heterogeneity and a generally low tumor mutational burden.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What features of the pediatric tumor microenvironment reduce immunotherapy effectiveness?",{"text":117,"@type":113},"The TME has scarce T-cell infiltration and abundant stromal cells with lymphocyte-suppressor and tumor-growth-promoting activity, weakening anti-tumor immune responses.",{"name":119,"@type":110,"acceptedAnswer":120},"What treatment direction does the review emphasize for pediatric solid tumors?",{"text":121,"@type":113},"Improving outcomes is likely to require modifying the TME while delivering novel, more effective therapeutic agents, including approaches that modulate immune cells in the TME.","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},330342,1790463462,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"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":41,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Review  \nPediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy  \nCristina Belgiovine 1,2, *, Kristiana Mebelli 2, Alessandro Raffaele 2, Marica De Cicco 3, Jessica Rotella 4, Paolo Pedrazzoli 5,6, Marco Zecca 4, Giovanna Riccipetitoni 1,2 and Patrizia Comoli 3, *  \nCitation: Belgiovine, C.; Mebelli, K.; Raffaele, A.; De Cicco, M.; Rotella, J.; Pedrazzoli, P.; Zecca, M.; Riccipetitoni, G.; Comoli, P. Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy. Int. J. Mol. Sci. 2024, 25, 3225. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25063225](doi.org/10.3390/ijms25063225)  \nAcademic Editor: Yong Teng  \nReceived: 13 December 2023  \nRevised: 26 February 2024  \nAccepted: 8 March 2024  \nPublished: 12 March 2024  \nCopyright: © 2024 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 Dipartimento di Scienze Clinico-Chirurgiche, Diagnostiche e Pediatriche, University of Pavia,  \n27100 Pavia, Italy  \n2 SC Chirurgia Pediatrica, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy  \n3 SSD Cell Factory e Center for Advanced Therapies, Department of Woman and Child Health, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy  \n4 SC Pediatric Hematology/Oncology, Department of Woman and Child Health, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy  \n5 Medical Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy  \n6 Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy  \n* Correspondence: [c.belgiovine@smatteo.pv.it](c.belgiovine@smatteo.pv.it) (C.B.); [pcomoli@smatteo.pv.it](pcomoli@smatteo.pv.it) (P.C.)  \nAbstract: Despite advances in their diagnosis and treatment, pediatric cancers remain among the leading causes of death in childhood. The development of immunotherapies and other forms of targeted therapies has significantly changed the prognosis of some previously incurable cancers in the adult population. However, so far, the results in pediatric cohorts are disappointing, which is mainly due to differences in tumor biology, including extreme heterogeneity and a generally low tumor mutational burden. A central role in the limited efficacy of immunotherapeutic approaches is played by the peculiar characteristics of the tumor microenvironment (TME) in pediatric cancer, with the scarcity of tumor infiltration by T cells and the abundance of stromal cells endowed with lymphocyte suppressor and tumor-growth-promoting activity. Thus, progress in the treatment of pediatric solid tumors will likely be influenced by the ability to modify the TME while delivering novel, more effective therapeutic agents. In this review, we will describe the TME composition in pediatric solid tumors and illustrate recent advances in treatment for the modulation of immune cells belonging to the TME.  \nKeywords: pediatric solid tumor; tumor microenvironment; immunotherapy; CAR-T cells  \n1. Introduction  \nThe well-known role of T cells in the durable control of cancer has been impressively exploited in recent times through the therapeutic use of tumor-targeted advanced-therapy medicinal products (ATMPs), such as T cells that have been genetically modified to express chimeric antigen receptors (CARs) or natural T cell receptors (TCRs) bearing tumorassociated antigens [1] . Moreover, improved knowledge of cancer’s immune evasion mechanisms and host–tumor interactions [2] has led to the development of immune checkpoint inhibitors (ICIs), a class of agents that are able to counteract the suppressive effects of the tumor microenvironment (TME) on host immune cells. These compounds were able to achieve l","cbCaigrZ8uxQy5tH","https://ap.wps.com/l/cbCaigrZ8uxQy5tH","pdf",1313853,"English","# Introduction\n# Overview of Solid Cancers in Childhood\n# TME Composition and Clinical Modulation Strategies","[{\"question\":\"Why do pediatric immunotherapy results lag behind adult outcomes?\",\"answer\":\"Pediatric cohorts show disappointing results mainly due to tumor biological differences, including extreme heterogeneity and a generally low tumor mutational burden.\"},{\"question\":\"What features of the pediatric tumor microenvironment reduce immunotherapy effectiveness?\",\"answer\":\"The TME has scarce T-cell infiltration and abundant stromal cells with lymphocyte-suppressor and tumor-growth-promoting activity, weakening anti-tumor immune responses.\"},{\"question\":\"What treatment direction does the review emphasize for pediatric solid tumors?\",\"answer\":\"Improving outcomes is likely to require modifying the TME while delivering novel, more effective therapeutic agents, including approaches that modulate immune cells in the TME.\"}]","Pediatric Solid Cancers - Issue/Article - Review | PDF",1789988296,76]