[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-356823-105":3,"detail-sidebar-cat-0-en-105":85,"doc-detail-356823-en":135},{"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":78,"head_meta":80,"extra_data":82,"updated_unix":84},105,"en","the-resilient-subset-cancer-stem-cells-at-the-core-of-immunotherapy-resistance-review","The resilient subset: cancer stem cells at the core of immunotherapy resistance - Review","","Cancer stem cells (CSCs) represent a small cell population with the capacity to initiate and sustain tumor growth through self-renewal and differentiation. Their involvement in tumor progression, metastasis, and recurrence is closely linked to therapeutic resistance across conventional and emerging treatments, including immunotherapy. This review summarizes key molecular, cellular, and metabolic CSC properties and emphasizes immunomodulatory effects within signaling pathways, an immunosuppressive microenvironment, and stromal interactions. Evidence across clinical settings supports a stem tumor phenotype associated with poor outcomes and reduced immune checkpoint inhibitor responses, while proposing strategies such as vaccination, differentiation, cellular therapies, and combination approaches.",{"@graph":14,"@context":77},[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/the-resilient-subset-cancer-stem-cells-at-the-core-of-immunotherapy-resistance-review/356823/",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/the-resilient-subset-cancer-stem-cells-at-the-core-of-immunotherapy-resistance-review/356823.png","ImageObject",300,407,{"name":42,"@type":43},"Đào","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69,73],{"name":60,"@type":61,"acceptedAnswer":62},"What role do cancer stem cells play in immunotherapy resistance?","Question",{"text":63,"@type":64},"Cancer stem cells contribute to resistance by sustaining tumor growth and driving immunomodulatory effects that support immune evasion. The review links CSC-associated architecture to therapeutic failure, including reduced responses to immune checkpoint inhibition.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which tumor microenvironment components are emphasized in the proposed model?",{"text":68,"@type":64},"The model highlights key signaling pathways, a suppressive microenvironment, and stromal components that interact with CSCs. This triaxial framing is used to explain how stemness architecture contributes to immune escape and treatment failure.",{"name":70,"@type":61,"acceptedAnswer":71},"How does the review connect CSC phenotype with clinical outcomes?",{"text":72,"@type":64},"It presents evidence from diverse clinical settings showing a tight correlation between a stem tumor phenotype and poor outcomes. These include reduced survival rates and dampened response to immune checkpoint inhibitors.",{"name":74,"@type":61,"acceptedAnswer":75},"What therapeutic approaches does the review propose to disrupt cancer stemness?",{"text":76,"@type":64},"The review proposes interventions including vaccination against CSC antigens, differentiation therapies, cellular therapies, and combinatorial approaches. These strategies aim to disrupt the cancer stemness architecture underlying immunotherapeutic resistance.","https://schema.org",{"og:url":32,"og:type":79,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":81,"canonical":32},"index,follow",{"doc_id":83,"site_id":7},356823,1790858279,{"code":4,"msg":86,"data":87},"success",[88,92,96,100,105,110,114,119,124,127,131],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Exam",70,"exam",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},5,"Comic",60,"comic",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},6,"Technology",50,"technology",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},7,40,"healthcare",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},8,"Research & Report",30,"research-report",{"id":120,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":122,"slug":123},9,"Religion & Spirituality",20,"religion-spirituality",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":122,"slug":126},"World Cup","world-cup",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":128,"slug":130},10,"Lifestyle","lifestyle",{"id":132,"doc_module":4,"doc_module_name":25,"category_name":133,"show_sort_weight":101,"slug":134},19,"General","general",{"code":4,"msg":86,"data":136},{"doc_id":83,"user_id":137,"nickname":42,"user_avatar":138,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":144,"language":145,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":146,"faqs":147,"seo_title":148,"seo_description":12,"update_tm":149,"read_time":150},1374402968488,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Immunotherapy Advances, 2026, 6, ltag006 [https://doi.org/10.1093/immadv/ltag006](https://doi.org/10.1093/immadv/ltag006)  \n[Published: 6 May 2026](Published: 6 May 2026)  \nReview  \n| The resilient subset: cancer stem cells at the core of immunotherapy resistance\u003Cbr>Julián A. Gajón  1,2*, Diego Esperante3,4, Nahuel Ko3, Aaron Jimenez-Miranda3, Samira Muñoz-Cruz3, Ezequiel Fuentes-Panana5, Laura C. Bonifaz3,6* |\n| --- |\n| 1 Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, Ciudad de México, México\u003Cbr>2 Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México\u003Cbr>3 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México\u003Cbr>4 Plan de Estudios Combinados en Medicina (PECEM), Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, México 5 Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Ciudad de México, México\u003Cbr>6Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México\u003Cbr>*Corresponding authors. Julián A. Gajón, Unidad de Investigación Médica en Inmunología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, 06720, Ciudad de México, Mé[xico. E-mail:](xico. E-mail: yulian_18@comunidad. unam. mx)[ yulian_18@comunidad. unam. mx](xico. E-mail: yulian_18@comunidad. unam. mx); Laura C. Bonifaz, Coordinación de Investigación en Salud, Centro Médico\u003Cbr>Nacional Siglo XXI, Instituto Mexicano del Seguro Social, 06720, Ciudad de México, México. E-mail: [labonifaz@yahoo.com](labonifaz@yahoo.com)\u003Cbr>Abstract\u003Cbr>Cancer stem cells (CSCs) are a small subset of cells that possess unique characteristics, including the ability to initiate and sustain tumor growth, self-renew, and differentiate into various types of cancer cells. They play a crucial role in tumor progression, metastasis, and recurrence. In recent years, CSCs have garnered significant attention due to their involvement in therapeutic resistance to both conventional and novel cancer treatments, including immunotherapy. This review delves into the fundamental properties of CSCs, molecular, cellular, and metabolic, focusing particularly on their immunomodulatory effects. We propose a comprehensive model that reflects the involvement of CSCs in various interlinked contexts, including key signaling pathways, the suppressive microenvironment, and the surrounding stromal components. Through this triaxial conceptualization, we highlight the key role of the stemness-orchestrated architecture in contributing to therapeutic failure. We present evidence gathered from diverse clinical settings, demonstrating a tight correlation between a stem tumor phenotype and poor clinical outcomes, including reduced survival rates and dampened response to immune checkpoint inhibitors (ICB). Finally, we propose therapeutic interventions specifically designed to disrupt the architecture of cancer stemness. These include vaccination against CSC antigens, differentiation therapies, cellular therapies, and combinatorial approaches. In summary, this review apprises an integral, up-to-date perspective that redefines the role of CSCs, positioning them at the core of immunotherapeutic resistance.\u003Cbr>Keywords cancer stem cells, cancer signaling, immune evasion, immunotherapy resistance, therapeutic failure\u003Cbr>Abbreviations: ABC, ATP-binding cassette transporter; ALDH, aldehyde dehydrogenase; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; BMP, bone morphogenetic protein; BRCA, breast cancer; CAF, cancer-associated fibroblast; CAR-T, chimeric antigen receptor T cell; cDC1, conventional type 1 dendritic cell; CRC, colorectal carcinoma; CSC, cancer stem cell; CTL, cytotoxic T lymphocy","cbCaiuMiLxzqnhR5","https://ap.wps.com/l/cbCaiuMiLxzqnhR5","pdf",1123334,26,"English","# Abstract\n## Cancer stem cells and tumor progression\n## Immunomodulatory effects and resistance architecture\n## Clinical evidence and immune checkpoint outcomes\n## Therapeutic interventions targeting stemness","[{\"question\":\"What role do cancer stem cells play in immunotherapy resistance?\",\"answer\":\"Cancer stem cells contribute to resistance by sustaining tumor growth and driving immunomodulatory effects that support immune evasion. The review links CSC-associated architecture to therapeutic failure, including reduced responses to immune checkpoint inhibition.\"},{\"question\":\"Which tumor microenvironment components are emphasized in the proposed model?\",\"answer\":\"The model highlights key signaling pathways, a suppressive microenvironment, and stromal components that interact with CSCs. This triaxial framing is used to explain how stemness architecture contributes to immune escape and treatment failure.\"},{\"question\":\"How does the review connect CSC phenotype with clinical outcomes?\",\"answer\":\"It presents evidence from diverse clinical settings showing a tight correlation between a stem tumor phenotype and poor outcomes. These include reduced survival rates and dampened response to immune checkpoint inhibitors.\"},{\"question\":\"What therapeutic approaches does the review propose to disrupt cancer stemness?\",\"answer\":\"The review proposes interventions including vaccination against CSC antigens, differentiation therapies, cellular therapies, and combinatorial approaches. These strategies aim to disrupt the cancer stemness architecture underlying immunotherapeutic resistance.\"}]","The resilient subset: cancer stem cells at the core of immunotherapy resistance - Review | PDF",1790127493,66]