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This open-access review concentrates on immuno-oncology and clinical demands for improved options against hard-to-treat cancers. It summarizes advances in TCR-T cells, CAR-T cells, tumor-infiltrating lymphocytes, and natural killer cells, emphasizing tumor-recognition enhancement and protection of infused cells in the tumor microenvironment.",{"@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/harnessing-novel-strategies-and-cell-types-to-overcome-immune-tolerance-during-adoptive-cell-therapy-in-cancer/383591/",{"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/harnessing-novel-strategies-and-cell-types-to-overcome-immune-tolerance-during-adoptive-cell-therapy-in-cancer/383591.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What core problem does the review address in adoptive cell therapy?","Question",{"text":112,"@type":113},"It focuses on overcoming immune tolerance during adoptive cell therapy by improving therapeutic responses in the tumor microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which cell therapy types are discussed?",{"text":117,"@type":113},"The review discusses T cell receptor–T cells, CAR-T cells, tumor-infiltrating lymphocytes, and natural killer cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What strategies does the review highlight to improve outcomes?",{"text":121,"@type":113},"Strategies include enhancing tumor recognition and increasing the resilience of infused immune cells within the tumor microenvironment.","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},383591,1790413005,{"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":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"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},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Open access Review  \n Harnessing novel strategies and cell  \ntypes to overcome immune tolerance during adoptive cell therapy in cancer  \nShi Yong Neo  ,1,2 Shengli Xu  ,1,3 Joni Chong,1 Kong-Peng Lam  ,1,4,5 Jing Wu  6,7  \nTo cite: Neo SY, Xu S,  \nChong J, et al. Harnessing novel strategies and cell types to overcome immune tolerance during adoptive cell therapy in cancer. Journal for ImmunoTherapy of Cancer 2023;11:e006434 . doi:10 . 1136/ jitc-2022-006434  \nAccepted 09 April 2023  \n© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nDr Shi Yong Neo;  \nneo_shi_yong@immunol.a-star. [edu.sg](edu.sg)  \nDr Jing Wu; [wujing@sdu.edu.cn](wujing@sdu.edu.cn)  \nABSTRACT  \nCell therapy encompasses an expanding spectrum of cell-based regimes for the treatment of human ailments, such as the use of immune cells, in particular T cells, for combating tumors and the modulation of inflammatory immune responses. In this review, we focus on cell therapy in the immuno-oncology space, which is largely driven by interests and demands from the clinics for better solutions to target various hard-to-treat cancers. We discuss recent advances in various types of cell therapies, including T cell receptor-T cells, chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes and natural killer cells.  \nParticularly, the present review focuses on the strategies to improve therapeutic responses by either enhancing tumor recognition or the resilience of infused immune cells within tumor microenvironment. Finally, we discuss the potential of other innate or innate-like immune cell types currently being explored as promising CAR-cell alternatives that seek to address the limitations of conventional adoptive cell therapies.  \nINTRODUCTION  \nThe roots of modern immune cell therapy date back more than 40 years when lymphokineactivated killer cells were first generated and subsequently infused into patients harboring various types of metastatic cancers, demonstrating sustainable objective responses.1 Along with issues of inadequate efficacies being often reported, there are also concerns about its toxicity and the difficulty of obtaining the required cell numbers for transplantation that further drove the development of alternative adoptive cell transfers (ACTs) modalities.2 Although immune cells can be expanded with considerably high potency in mounting antitumor responses, the success of ACT is heavily dependent on critical prerequisites such as a favorable tumor microenvironment (TME) and sufficient tumor immunogenicity. This is why the success of various cell therapies is largely limited to hematological malignancies.3  \nOften in solid tumors, the frailty of immune cells is a result of the harsh TME, which is populated by multiple types of immune-suppressive factors, and the intense competition for  \nnutrients among highly metabolic tumor cells, cancer-associated fibroblasts and inflammatory immune cells.4 As a result, advancements in conferring cytoprotection and intrinsic resilience to cell therapy products are constantly being developed to overcome such obstacles (figure 1). However, these novel modalities to modify and generate superior immune cells are also hindered by the limited availability of good manufacturing practice (GMP) grade reagents, and the cost-effectiveness of product manufacturing.5 In contrast to hematological cancers, solid tumors often have high antigenic heterogeneity and lack tumor-specific antigens (TSAs) suitable for targeted-chimeric antigen receptor (CAR) design.4 Therefore, as seen with combination therapies, means of enhancing antitumor responses by epitope spreading are often necessary. Inducing immunogenic cell death, the release of tumor-associated antigens (TAAs) could further boost endogenous immune responses alongside the infused killer cells.5 In this rev","cbCaihpDkdMWdrLb","https://ap.wps.com/l/cbCaihpDkdMWdrLb","pdf",779430,"English","# Abstract\n# Introduction\n# Genetically engineered T cell receptors (TCRs) for enhanced tumor recognition","[{\"question\":\"What core problem does the review address in adoptive cell therapy?\",\"answer\":\"It focuses on overcoming immune tolerance during adoptive cell therapy by improving therapeutic responses in the tumor microenvironment.\"},{\"question\":\"Which cell therapy types are discussed?\",\"answer\":\"The review discusses T cell receptor–T cells, CAR-T cells, tumor-infiltrating lymphocytes, and natural killer cells.\"},{\"question\":\"What strategies does the review highlight to improve outcomes?\",\"answer\":\"Strategies include enhancing tumor recognition and increasing the resilience of infused immune cells within the tumor microenvironment.\"}]","Harnessing novel strategies and cell types to overcome immune tolerance during adoptive cell therapy in cancer | PDF",1790257989,25]