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This review surveys NK cell-based immunotherapeutic approaches, including cytokine therapy, immune checkpoint inhibition, antibody-dependent cellular cytotoxicity, and adoptive cell transfer, summarizing clinical potential and constraints. It analyzes challenges in NK cell expansion, genetic engineering such as CAR-NK development, and tumor microenvironment-driven immunosuppression, then evaluates combination regimens, nanotechnology delivery, and personalized medicine to address current barriers.",{"@graph":69,"@context":127},[70,84,106],{"@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/natural-killer-cell-based-immunotherapies-for-colorectal-cancer-current-strategies-challenges-and-future-perspectives/370900/",{"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/natural-killer-cell-based-immunotherapies-for-colorectal-cancer-current-strategies-challenges-and-future-perspectives/370900.png","ImageObject",300,407,{"name":92,"@type":93},"Franzy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"Why are natural killer (NK) cells considered promising for colorectal cancer immunotherapy?","Question",{"text":113,"@type":114},"NK cells can recognize and eliminate tumor cells based on innate immune mechanisms without prior sensitization, which supports their potential as therapeutic agents for colorectal cancer.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What immunotherapeutic strategies are reviewed for NK-cell based treatment?",{"text":118,"@type":114},"The review covers cytokine therapy, immune checkpoint inhibition, antibody-dependent cellular cytotoxicity, and adoptive cell transfer, describing both clinical potential and limitations.",{"name":120,"@type":111,"acceptedAnswer":121},"What major challenges limit the effectiveness of NK cell therapies?",{"text":122,"@type":114},"Key challenges include difficulties in NK cell expansion, the complexities of genetic engineering (notably CAR-NK development), and immunosuppression mediated by the tumor microenvironment.",{"name":124,"@type":111,"acceptedAnswer":125},"What future directions does the review emphasize?",{"text":126,"@type":114},"Future work focuses on standardized manufacturing protocols, strategies to improve NK cell persistence, and clinical validation of emerging technologies, alongside approaches such as combination therapies, nanotechnology-enhanced delivery, and personalized medicine.","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},370900,1790219167,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":144,"language":145,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":146,"faqs":147,"seo_title":148,"seo_description":67,"update_tm":149,"read_time":150},2336478945519,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","| W | J | G | World Journal of\u003Cbr>Gastroenterology |\n| --- | --- | --- | --- |\n\nSubmit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Gastroenterol 2025 September 14; 31(34): 110051  \nDOI: 10.3748/wjg.v31.i34.110051 ISSN 1007-9327 (print) ISSN 2219-2840 (online)  \nREVIEW  \nNatural killer cell-based immunotherapies for colorectal cancer: Current strategies, challenges, and future perspectives  \nXiao-Jun Zhang, Yan Yu, Jing-Yu Li, Yu-Zhu Yan, Sha-Sha Jiang, Yi Zhang, Qin Fei, Yi-Ran Zhang, Yong-Xin Zhao, Lei Guo, Jing Lv, He-Ping Zhao  \nSpecialty type: Gastroenterology and hepatology  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade B, Grade B  \nNovelty: Grade B, Grade B  \nCreativity or Innovation: Grade C, Grade C  \nScientific Significance: Grade B, Grade C  \nP-Reviewer: He P, PhD, Assistant Professor, China; Wang T, MD, China  \nReceived: May 28, 2025  \nRevised: June 21, 2025  \nAccepted: August 18, 2025  \nPublished online: September 14, 2025  \nProcessing time: 100 Days and 0.3 Hours  \nXiao-Jun Zhang, Yan Yu, Yu-Zhu Yan, Sha-Sha Jiang, Yi Zhang, Yi-Ran Zhang, Yong-Xin Zhao, Jing Lv, He-Ping Zhao, Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China  \nJing-Yu Li, Highway College, Chang’an University, Xi’an 710054, Shaanxi Province, China  \nQin Fei, Department of Anesthesiology, The Third People’s Hospital of Chengdu, Chengdu 610031, Sichuan Province, China  \nLei Guo, Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China  \nCo-first authors: Xiao-Jun Zhang and Yan Yu.  \nCo-corresponding authors: Jing Lv and He-Ping Zhao.  \nCorresponding author: Jing Lv, MD, Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, No. 555 Youyi East Road, Xi’an 710054, Shaanxi Province, China.  \n[lvjing-1219@163.com](lvjing-1219@163.com)  \nAbstract  \nNatural killer (NK) cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization. In this review, NK cell-based immunotherapeutic approaches, including cytokine therapy, immune checkpoint inhibition, antibody-dependent cellular cytotoxicity, and adoptive cell transfer, are comprehensively examined, and their respective clinical potential and limitations are highlighted. We discuss critical challenges in NK cell expansion, genetic engineering (particularly chimeric antigen receptor-NK development), and tumor microenvironment-mediated immunosuppression. Furthermore, we explore innovative strategies such as combination therapies, nanotechnology-enhanced delivery, and personalized medicine approaches that aim to overcome the current barriers. The review concludes with future directions emphasizing the need for standardized manufacturing protocols, new strategies to improve NK cell persistence, and clinical validation of emerging technologies, positioning NK cell immunotherapy as a transformative modality for colorectal cancer treatment.  \n WJG  [https://www.wjgnet.com](https://www.wjgnet.com) 1 September 14, 2025  Volume 31  Issue 34   \nZhang XJ et al. NK cells in CRC immunotherapy  \nKey Words: Natural killer cells; Colorectal cancer; Immunotherapy; Immunosuppression; Tumor microenvironment  \n©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.  \nCore Tip: Natural killer (NK) cell-based immunotherapy represents a breakthrough approach for treating colorectal cancer (CRC), particularly for microsatellite-stable tumors resistant to conventional treatments. Currently employed strategies, including cytokine therapy, checkpoint inhibition, and chimeric antigen receptor-NK cell therapy, show promise in CRC treatment, but manufacturing challenges and the immunosu","cbCaiv403xoKhboC","https://ap.wps.com/l/cbCaiv403xoKhboC","pdf",2429927,21,"English","# Natural killer cell-based immunotherapies for colorectal cancer\n## Current strategies, challenges, and future perspectives","[{\"question\":\"Why are natural killer (NK) cells considered promising for colorectal cancer immunotherapy?\",\"answer\":\"NK cells can recognize and eliminate tumor cells based on innate immune mechanisms without prior sensitization, which supports their potential as therapeutic agents for colorectal cancer.\"},{\"question\":\"What immunotherapeutic strategies are reviewed for NK-cell based treatment?\",\"answer\":\"The review covers cytokine therapy, immune checkpoint inhibition, antibody-dependent cellular cytotoxicity, and adoptive cell transfer, describing both clinical potential and limitations.\"},{\"question\":\"What major challenges limit the effectiveness of NK cell therapies?\",\"answer\":\"Key challenges include difficulties in NK cell expansion, the complexities of genetic engineering (notably CAR-NK development), and immunosuppression mediated by the tumor microenvironment.\"},{\"question\":\"What future directions does the review emphasize?\",\"answer\":\"Future work focuses on standardized manufacturing protocols, strategies to improve NK cell persistence, and clinical validation of emerging technologies, alongside approaches such as combination therapies, nanotechnology-enhanced delivery, and personalized medicine.\"}]","Natural killer cell-based immunotherapies for colorectal cancer - Current strategies, challenges, and future perspectives | PDF",1790190782,53]