[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-451515-105":59,"doc-detail-451515-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","tmem33-deletion-potentiates-anti-tumor-cd8-t-cell-immunity","TMEM33 deletion potentiates anti-tumor CD8+ T cell immunity","","Improving responses to cancer immunotherapies requires deeper insight into the cellular mechanisms governing T cell-mediated anti-tumor immunity. TMEM33 is an endoplasmic reticulum-resident transmembrane protein enriched across multiple tumor types, with reported functions in anti-viral immunity and in calcium and lipid homeostasis, but its role in tumor immunosurveillance remained unknown. Using murine genetic models, host TMEM33 constrains anti-tumor CD8+ T cell responses.",{"@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/tmem33-deletion-potentiates-anti-tumor-cd8-t-cell-immunity/451515/",{"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/tmem33-deletion-potentiates-anti-tumor-cd8-t-cell-immunity/451515.png","ImageObject",300,407,{"name":92,"@type":93},"McQueen","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is TMEM33, and why was its role in tumor immunity investigated?","Question",{"text":112,"@type":113},"TMEM33 is an endoplasmic reticulum-resident transmembrane protein enriched across multiple tumor types. Although it has roles in anti-viral immunity and in calcium/lipid homeostasis, its contribution to tumor immunosurveillance was previously unknown.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does TMEM33 deletion affect anti-tumor CD8+ T cell responses in mouse models?",{"text":117,"@type":113},"Constitutive Tmem33-/- mice show delayed melanoma tumor growth and increased CD8+ T cell infiltration. Tumor CD8+ compartments are enriched for TCF-1+ PD-1+ progenitor-exhausted (Tpex) cells, with higher effector function and reduced exhaustion.",{"name":119,"@type":110,"acceptedAnswer":120},"Does TMEM33 deletion influence adoptive cell therapy outcomes?",{"text":121,"@type":113},"Yes. TMEM33 deletion enhances polyclonal activation of naive CD8+ T cells ex vivo, promotes Tpex accumulation among adoptively transferred OT-I cells, and improves the potency of ex vivo-expanded OT-I cells in controlling tumor growth during adoptive cell therapy.","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},451515,1790958805,{"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":34,"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,"preview_page_count":4},5909890329169,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","bioRxiv preprint doi: [https://doi.org/10.64898/2026.01.01.697288](https://doi.org/10.64898/2026.01.01.697288); this version posted January 2, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \nTMEM33 deletion potentiates anti-tumor CD8+ T cell immunity  \nMatthew T Jackson 1,2 , Tianming Zhao 1,2 , Gusztav Milotay 1 , Isabela Pedroza-Pacheco2,3 , Yanshu Cai2 , Claire Willis2 , Su M Phyu 1,2 , Bruno Beernaert 1,2 , Jamie TW Kwon1,2 , Hala Estephan 1 , Vinnycius Pereira Almeida4 , Maria Aggelakopoulou2 , Silvia Panetti4 , Christian Zierhut5 , Tim Elliott2 , Eleni Adamopoulou2 , Jan Rehwinkel6 , Malcolm JW Sim2 , Amit Grover7 , Dmitry I Gabrilovich8 , Benjamin P Fairfax 1 , Eric Honoré9 , David R Withers2 , John C Christianson 10 , Eileen E Parkes 1,2  \n1 Department of Oncology, University of Oxford, Oxford, UK  \n2 Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK  \n3 Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK  \n4 Ludwig Institute for Cancer Research, University of Oxford, UK  \n5 The Institute of Cancer Research, London, UK  \n6 MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK  \n7 Immuno-Oncology, Circuits-Engagers & Cell Therapy, Oncology R&D, AstraZeneca, Cambridge,  \nUK  \n8 Immuno-Oncology, Circuits-Engagers & Cell Therapy, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA  \n9 Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France  \n10 Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK  \nCorresponding author:  \nAssociate Professor Eileen E Parkes  \n[Eileen.parkes@oncology.ox.ac.uk](Eileen.parkes@oncology.ox.ac.uk)  \nKey words: TMEM33, cancer immunity, endoplasmic reticulum, T cell, Tpex  \nOne sentence summary: TMEM33 intrinsically limits progenitor exhausted CD8+ T cells, scales antitumor responses and predicts melanoma patient survival.  \nbioRxiv preprint doi: [https://doi.org/10.64898/2026.01.01.697288](https://doi.org/10.64898/2026.01.01.697288); this version posted January 2, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \nDECLARATIONS  \nM.T.J. received doctoral studentship funding from AstraZeneca. E. E. P. has served on advisory boardsand performed consultancy for Boehringer Ingelheim, Curadev, InhaTarget, and AkamisBio. She is an employee of the University of Oxford, which has received funding or other research support from AstraZeneca and [STIpe Therapeutics. V.P.A. is](STIpe Therapeutics. V.P.A. is) employed part-time as an Immunology Scientist at Infinitopes. T. E. acts as a consultant for Dark Blue Therapeutics. E.A. has received funding or other research support from Moderna and GSK. A.G. and D. I.G. are employees and shareholders of AstraZeneca. In the last three years, B. P. F. has performed consultancy for NICE Consultancy, Roche, Pathios, UCB, and TCypher, and has received speaker fees from GSK, UCB, and BMS, all outside the submitted work. All other authors declare no competing interests.  \nbioRxiv preprint doi: [https://doi.org/10.64898/2026.01.01.697288](https://doi.org/10.64898/2026.01.01.697288); this version posted January 2, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in p","cbCaip7idg8Ojre4","https://ap.wps.com/l/cbCaip7idg8Ojre4","pdf",24332300,46,"English","# Abstract\n## Background\n## Methods and key findings\n## Therapeutic implications","[{\"question\":\"What is TMEM33, and why was its role in tumor immunity investigated?\",\"answer\":\"TMEM33 is an endoplasmic reticulum-resident transmembrane protein enriched across multiple tumor types. Although it has roles in anti-viral immunity and in calcium/lipid homeostasis, its contribution to tumor immunosurveillance was previously unknown.\"},{\"question\":\"How does TMEM33 deletion affect anti-tumor CD8+ T cell responses in mouse models?\",\"answer\":\"Constitutive Tmem33-/- mice show delayed melanoma tumor growth and increased CD8+ T cell infiltration. Tumor CD8+ compartments are enriched for TCF-1+ PD-1+ progenitor-exhausted (Tpex) cells, with higher effector function and reduced exhaustion.\"},{\"question\":\"Does TMEM33 deletion influence adoptive cell therapy outcomes?\",\"answer\":\"Yes. TMEM33 deletion enhances polyclonal activation of naive CD8+ T cells ex vivo, promotes Tpex accumulation among adoptively transferred OT-I cells, and improves the potency of ex vivo-expanded OT-I cells in controlling tumor growth during adoptive cell therapy.\"}]","TMEM33 deletion potentiates anti-tumor CD8+ T cell immunity | PDF",1790735318,116]