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This mini review focuses on cellular immunotherapies, emphasizing CAR-T therapy and its evolution, while outlining major resistance mechanisms including immune evasion, antigen loss, immune checkpoint upregulation, and immunosuppressive tumor microenvironment effects. It also considers engineered NK cells and macrophages, and evaluates strategies like combination approaches, gene editing, and nanotechnology to improve targeted delivery and effectiveness.",{"@graph":69,"@context":123},[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/advancements-in-cellular-immunotherapy-overcoming-resistance-in-lung-and-colorectal-cancer/370275/",{"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/advancements-in-cellular-immunotherapy-overcoming-resistance-in-lung-and-colorectal-cancer/370275.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is CAR-T therapy less effective in lung and colorectal cancers than in blood cancers?","Question",{"text":113,"@type":114},"Solid tumors create immunosuppressive tumor microenvironments, promote antigen loss, and upregulate immune checkpoints such as PD-L1, which reduce CAR-T recognition and T-cell function.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What resistance mechanisms does the review highlight for solid tumors?",{"text":118,"@type":114},"Key mechanisms include immune evasion, antigen loss/downregulation, immune checkpoint upregulation, and microenvironment immunosuppression driven by cells and factors such as Tregs, MDSCs, tumor-associated macrophages, and TGF-β.",{"name":120,"@type":111,"acceptedAnswer":121},"What approaches are discussed to overcome resistance in solid tumor immunotherapy?",{"text":122,"@type":114},"The review covers dual-CAR-T development, off-the-shelf allogeneic strategies and NK cell approaches, and cutting-edge methods including combination therapies, gene editing, and nanotechnology-based targeted drug delivery.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},370275,1790468682,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"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},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","TYPE Mini Review  \nPUBLISHED 05 February 2025  \nDOI 10.3389/fimmu.2025.1554256  \nOPEN ACCESS  \nEDITED BY  \nYu ’e Liu,  \nHarvard Medical School, United States  \nREVIEWED BY  \nJin-Ming Zhang,  \nUniversity of Texas Health Science Center at Houston, United States  \nYunlin Zhang,  \nMemorial Sloan Kettering Cancer Center, United States  \n*CORRESPONDENCE  \nXiaoqin An  \n [anxiaoqin10@163.com](anxiaoqin10@163.com)[ ](anxiaoqin10@163.com)Juan Liu  \n [liujuan8291@163.com](liujuan8291@163.com)  \n†These authors have contributed equally to this work  \nRECEIVED 01 January 2025  \nACCEPTED 17 January 2025  \nPUBLISHED 05 February 2025  \nCITATION  \nQin L, Li Y, Liu J and An X (2025)  \nAdvancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer.  \nFront. Immunol. 16:1554256 .  \ndoi: 10.3389/fimmu.2025.1554256  \nCOPYRIGHT  \n© 2025 Qin, Li, Liu and An. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nAdvancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer  \nLijuan Qin 1†, Yuan Li 2†, Juan Liu 3* and Xiaoqin An 2*  \n1 Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China, 2 Department of Respiratory Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China, 3 Department of Special needs Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China  \nImmunotherapy has revolutionized cancer treatment, offering hope for patients with otherwise treatment-resistant tumors. Among the most promising approaches are cellular therapies, particularly chimeric antigen receptor T-cell (CAR-T) therapy, which has shown remarkable success in hematologic malignancies. However, the application of these therapies to solid tumors, such as lung and colorectal cancers, has faced significant challenges. Tumor resistance mechanisms—ranging from immune evasion, antigen loss, and immune checkpoint upregulation, to tumor microenvironment immunosuppression—remain major obstacles. This mini-review highlights the latest advancements in tumor immunotherapy, with a focus on cellular therapies, and addresses the resistance mechanisms that hinder their effectiveness in lung and colorectal cancers. We examine the evolution of CAR-T cell therapy, as well as the potential of engineered natural killer (NK) cells and macrophages in solid tumor treatment. The review also explores cutting-edge strategies aimed at overcoming resistance, including combination therapies, gene editing technologies, and nanotechnology for targeted drug delivery. By discussing the molecular, cellular, and microenvironmental factors contributing to resistance, we aim to provide a comprehensive overview of how these challenges can be overcome, paving the way for more effective, personalized immunotherapies in lung and colorectal cancer treatment.  \nKEYWORDS  \nimmunotherapy, CAR-T cells, lung cancer, colorectal cancer, resistance mechanisms  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nImmunotherapy has revolutionized cancer treatment, providing novel approaches that harness the body’s immune system to fight cancer. Among these, cellular immunotherapies, particularly chimeric","cbCais8ukWs7aPXm","https://ap.wps.com/l/cbCais8ukWs7aPXm","pdf",1212056,"English","# Introduction\n## Cellular immunotherapies and CAR-T in solid tumors\n## Resistance mechanisms in the tumor microenvironment\n## Strategies to overcome resistance","[{\"question\":\"Why is CAR-T therapy less effective in lung and colorectal cancers than in blood cancers?\",\"answer\":\"Solid tumors create immunosuppressive tumor microenvironments, promote antigen loss, and upregulate immune checkpoints such as PD-L1, which reduce CAR-T recognition and T-cell function.\"},{\"question\":\"What resistance mechanisms does the review highlight for solid tumors?\",\"answer\":\"Key mechanisms include immune evasion, antigen loss/downregulation, immune checkpoint upregulation, and microenvironment immunosuppression driven by cells and factors such as Tregs, MDSCs, tumor-associated macrophages, and TGF-β.\"},{\"question\":\"What approaches are discussed to overcome resistance in solid tumor immunotherapy?\",\"answer\":\"The review covers dual-CAR-T development, off-the-shelf allogeneic strategies and NK cell approaches, and cutting-edge methods including combination therapies, gene editing, and nanotechnology-based targeted drug delivery.\"}]","Advancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer | PDF",1790187713,23]