[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-346040-105":59,"doc-detail-346040-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-of-cancer-without-induction-of-autoimmunity-cd6-as-a-therapeutic-target","Immunotherapy of cancer without induction of autoimmunity - CD6 as a therapeutic target","","A question-and-answer mini review examines CD6 as a cancer immunotherapy target by linking its biology to therapeutic mechanisms. CD6 is a surface glycoprotein on most T cells and subsets of B and NK cells, acting within the immunological synapse to modulate TCR signaling through interacting ligands, epitopes, kinases, and adapter proteins. The review highlights anti-CD6 monoclonal antibodies that internalize CD6 and reshape gene expression in CD8+ T cells and NK cells to enhance cytotoxicity while potentially avoiding autoimmune complications typical of checkpoint inhibitors.",{"@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-of-cancer-without-induction-of-autoimmunity-cd6-as-a-therapeutic-target/346040/",{"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-of-cancer-without-induction-of-autoimmunity-cd6-as-a-therapeutic-target/346040.png","ImageObject",300,407,{"name":92,"@type":93},"Genevieve","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 is CD6 and where is it expressed in the immune system?","Question",{"text":112,"@type":113},"CD6 is a cell surface glycoprotein expressed by almost all T cells, a small subset of B cells, and a substantial proportion of human natural killer (NK) cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How might anti-CD6 therapy enhance anti-cancer responses?",{"text":117,"@type":113},"Anti-CD6 monoclonal antibodies rapidly internalize CD6 and alter gene expression in CD8+ T cells and NK cells, augmenting cytotoxicity against human cancer cells across multiple neoplasms.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is CD6 being explored as a cancer target instead of relying on checkpoint inhibitors?",{"text":121,"@type":113},"The review explores whether targeting CD6 could avoid autoimmune complications commonly encountered with checkpoint inhibitor treatment of cancer.","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},346040,1790156196,{"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":34,"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},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","TYPE Mini Review  \nPUBLISHED 11 August 2026  \nDOI 10.3389/fimmu.2026.1845422  \nOPEN ACCESS  \nEDITED BY  \nZohreh Amoozgar,  \nAstraZeneca & Alexion, United States  \nREVIEWED BY  \nFrancisco Lozano,  \nHospital Clnic de Barcelona, Spain Linzhu Zhang,  \nSoutheast University, China  \n*CORRESPONDENCE  \nMikel Gurrea-Rubio  \n [mikelg@med.umich.edu](mikelg@med.umich.edu)[ ](mikelg@med.umich.edu)David A. Fox  \n [dfox@med.umich.edu](dfox@med.umich.edu)[ ](dfox@med.umich.edu)RECEIVED 01 April 2026 REVISED 21 July 2026 ACCEPTED 28 July 2026 PUBLISHED 11 August 2026  \nCITATION  \nFox DA and Gurrea-Rubio M (2026) Immunotherapy of cancer without induction of autoimmunity – CD6 as a therapeutic target.  \nFront. Immunol. 17:1845422 .  \ndoi: 10.3389/fimmu.2026.1845422  \nCOPYRIGHT  \n© 2026 Fox and Gurrea-Rubio. This is an open-access 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.  \nImmunotherapy of cancer without induction of autoimmunity – CD6 as a therapeutic target  \nDavid A. Fox* and Mikel Gurrea-Rubio*  \nDivision of Rheumatology and Program in Translational Immunology, University of Michigan, Ann Arbor, Michigan, MI, United States  \nThe CD6 cell surface glycoprotein is expressed by almost all T cells, a small subset of B cells and a substantial proportion of human natural killer (NK) cells. CD6 has multiple ligands and multiple functional epitopes. It is a component of the immunological synapse, and can positively or negatively influence signal transduction in T cells through complex interactions with multiple kinases and adapter molecules. Antibodies to CD6 are effective in the treatment of autoimmune diseases in experimental systems and in humans. The recent discovery that CD318 (CDCP1), a driver molecule in many cancers, is a ligand for CD6 has prompted investigation of CD6 as a possible new target for immunotherapy of cancer. Amonoclonal antibody to CD6 rapidly internalizes CD6 and alters gene expression in CD8+ T cells and NK cells to augment the cytotoxicity of human lymphocytes to human cancer cells from a range of neoplasms. This review, using a question and answer format, describes recent work on anti-CD6 as a candidate immunotherapy for cancer as well as relevant advances in our understanding of other aspects of the biology of CD6, and explores the possibility that this approach could avoid the autoimmune complications that are encountered with checkpoint inhibitor treatment of cancer.  \nKEYWORDS  \nautoimmunity, cancer immunotherapy, CD6, CD8+ T cells, immune checkpoint inhibitors, NK cells, regulatory T cells  \nWhat is the role of CD6 in the thymus?  \nThe gradual increase in CD6 expression as developing thymocytes progress through their differentiation stages in the thymus closely parallels the gradual increase in expression of the CD3/TCR complex (1, 2). This suggests that CD6 may functionally interact with CD3/ TCR during negative and positive selection. Moreover, CD6 expression on thymocytes directly correlates with the expression of the positive selection marker CD69 (1) .  \nThe action of CD6 in the thymus needs to be understood in the context of experiments that used CD6-/- mice in models of autoimmune disease, that showed striking clinical protection, and inhibition of the development of Th effector cells that could secrete cytokines such as gamma-interferon, IL-17 and IL-9 . Similar results were obtained with the use of an anti-CD6 monoclonal antibody (mAb) in CD6-humanized mice (3–5) . These results are consistent with the suggestion that CD6 enhances positive selection in the thymus. In the absence of CD6 mildly autoreactive thymocytes that had evaded n","cbCaivcE5DcCLfRZ","https://ap.wps.com/l/cbCaivcE5DcCLfRZ","pdf",1004951,"English","# Immunotherapy of cancer without induction of autoimmunity – CD6 as a therapeutic target\n## What is the role of CD6 in the thymus?\n## How does CD6 affect the response of T cells following activation through the T cell antigen receptor/CD3 (TCR/CD3) complex?","[{\"question\":\"What is CD6 and where is it expressed in the immune system?\",\"answer\":\"CD6 is a cell surface glycoprotein expressed by almost all T cells, a small subset of B cells, and a substantial proportion of human natural killer (NK) cells.\"},{\"question\":\"How might anti-CD6 therapy enhance anti-cancer responses?\",\"answer\":\"Anti-CD6 monoclonal antibodies rapidly internalize CD6 and alter gene expression in CD8+ T cells and NK cells, augmenting cytotoxicity against human cancer cells across multiple neoplasms.\"},{\"question\":\"Why is CD6 being explored as a cancer target instead of relying on checkpoint inhibitors?\",\"answer\":\"The review explores whether targeting CD6 could avoid autoimmune complications commonly encountered with checkpoint inhibitor treatment of cancer.\"}]","Immunotherapy of cancer without induction of autoimmunity - CD6 as a therapeutic target | PDF",1790059816,18]