[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-340942-105":59,"doc-detail-340942-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","immunotherapy-resistance-in-solid-tumors-mechanisms-and-potential-solutions","Immunotherapy resistance in solid tumors - mechanisms and potential solutions","","Immunotherapies have transformed solid-tumor management, yet cancers deploy diverse biological programs that drive resistance. Mechanisms span antigen presentation and immunoregulation, metabolic rewiring, and exploitation of the tumor microenvironment, enabling cancers to evade both natural immunity and therapeutic pressure. This review organizes resistance into primary (innate) and secondary (acquired) pathways and evaluates established as well as emerging interventions that aim to overcome immunotherapy resistance, supporting practice-changing research directions.",{"@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/immunotherapy-resistance-in-solid-tumors-mechanisms-and-potential-solutions/340942/",{"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/immunotherapy-resistance-in-solid-tumors-mechanisms-and-potential-solutions/340942.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-22",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},"What causes immunotherapy resistance in solid tumors according to the review?","Question",{"text":112,"@type":113},"Resistance arises from multiple biological mechanisms, including altered antigen presentation, immunoregulation, metabolic changes, and manipulation of the tumor microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the review classify resistance to immunotherapies?",{"text":117,"@type":113},"It distinguishes primary (innate) resistance based on baseline tumor characteristics from secondary (acquired) resistance arising after initial sensitivity.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic strategies does the review consider for overcoming immunotherapy resistance?",{"text":121,"@type":113},"It discusses available and emerging approaches aimed at blocking or reversing the mechanisms tumors use to evade both natural immunity and immunotherapies.","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},340942,1790315715,{"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},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","CANCER BIOLOGY & THERAPY  \n2024, VOL. 25, NO. 1, 2315655 [https://doi.org/10.1080/15384047.2024.2315655](https://doi.org/10.1080/15384047.2024.2315655)  \nREVIEW  \nImmunotherapy resistance in solid tumors: mechanisms and potential solutions  \nDaniel S. Lefler a, Steven A. Manobianco b, and Babar Bashir b,c  \naDepartment of Medicine, Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; bDepartment of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA; cDepartment of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA  \nABSTRACT  \nWhile the emergence of immunotherapies has fundamentally altered the management of solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range of cellular activities – from modification of traditional paradigms of immunity via antigen presentation and immunoregulation to metabolic modifications and manipulation of the tumor microenvironment. Intervening on these intricate processes may provide clinical benefit inpatients with solid tumors by overcoming resistance to immunotherapies, which is why it has become an area of tremendous research interest with practice-changing implications. This review details the major ways cancers avoid both natural immunity and immunotherapies through primary (innate) and secondary (acquired) mechanisms of resistance, and it considers available and emerging therapeutic approaches to overcoming immunotherapy resistance.  \nARTICLE HISTORY  \nReceived 24 July 2023 Revised 14 January 2024 Accepted 4 February 2024  \nKEYWORDS  \nImmunoresistance; cancer treatment; immune checkpoint inhibitors; cytokines; tumor microenvironment  \nIntroduction  \nCancer immunotherapies have captured the attention of the scientific and lay communities alike, yet many obstacles continue to limit their use in solid tumors. Impressive clinical successes of immune checkpoint inhibitors (ICIs) have been notched in immunologically “hot” tumors like melanoma, non-small cell lung cancer (NSCLC), cutaneous squamous cell carcinoma, and renal cell carcinoma. Meanwhile, the efficacy of cancer vaccines and adoptive T cell treatments like tumor infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells have been much more tempered, noting the latter has enjoyed particular success in hematologic malignancies.1 T cell engagers (TCEs), and specifically T cell engaging bispecific antibodies (e.g., BiTEⓇ), have recently become a much more active area of investigation in solid tumors, as well, though the large-scale translation of this technology to clinical practice is limited and is most notably characterized by tabentafusp-tebn for uveal melanoma.2,3  \nThe majority of presently available (and investigational) cancer immunotherapies highlight the overarching importance of anti-tumor T cell activity. This is because CD8-expressing cytotoxic T lymphocytes (CTLs) are ultimately responsible for the final step in the process of immune regulation of cancers: killing tumor cells. They perform this task through two main processes. The most well-described is the secretion of the pore-forming protein perforin, which allows co-secreted granzymes to enter the target cell and induce apoptosis.4 Additionally, CTL-induced Fas signaling results in Fas clustering on target cell membranes and the subsequent recruitment of the Fas-associated death domain (FADD), inducing apoptosis through caspases.5  \nAlthough accurate, this characterization oversimplifies immunologic tumor death. In reality, the machinations that set the stage for the interaction between tumors and CTLs are carefully coordinated. These are summarized in Figure 1 and explored more in-depth in the following review. Recognition of cancer-related antigens is key to identifying tumors as “nonself” and thus immunogenic, involving","cbCaicYtPH63qOV1","https://ap.wps.com/l/cbCaicYtPH63qOV1","pdf",1097129,17,"English","# Introduction\n## Mechanisms of immune evasion and resistance\n## Primary (innate) vs secondary (acquired) resistance\n## Therapeutic approaches to overcome resistance","[{\"question\":\"What causes immunotherapy resistance in solid tumors according to the review?\",\"answer\":\"Resistance arises from multiple biological mechanisms, including altered antigen presentation, immunoregulation, metabolic changes, and manipulation of the tumor microenvironment.\"},{\"question\":\"How does the review classify resistance to immunotherapies?\",\"answer\":\"It distinguishes primary (innate) resistance based on baseline tumor characteristics from secondary (acquired) resistance arising after initial sensitivity.\"},{\"question\":\"What therapeutic strategies does the review consider for overcoming immunotherapy resistance?\",\"answer\":\"It discusses available and emerging approaches aimed at blocking or reversing the mechanisms tumors use to evade both natural immunity and immunotherapies.\"}]","Immunotherapy resistance in solid tumors - mechanisms and potential solutions | PDF",1790039642,43]