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This study shows the antifungal drug sulconazole (SCZ) suppresses PD-1 expression on activated PBMCs and T cells at both RNA and protein levels. SCZ represses NF-kB and calcium signaling implicated in PD-1 induction, while additionally reducing cancer cell proliferation and migration and tumor growth capacity in zebrafish embryos.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/sulconazole-inhibits-pd-1-expression-in-immune-cells-and-cancer-cells-malignant-phenotype-through-nf-kb-and-calcium-activity-repression/342419/",{"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/sulconazole-inhibits-pd-1-expression-in-immune-cells-and-cancer-cells-malignant-phenotype-through-nf-kb-and-calcium-activity-repression/342419.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What effect does sulconazole have on PD-1 expression in immune cells?","Question",{"text":112,"@type":113},"Sulconazole inhibits PD-1 expression on activated PBMCs and T cells at both RNA and protein levels.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which signaling pathways are repressed by sulconazole in relation to PD-1?",{"text":117,"@type":113},"Sulconazole represses NF-kB and calcium signaling, both involved in inducing PD-1.",{"name":119,"@type":110,"acceptedAnswer":120},"How does sulconazole impact cancer cell behavior and tumor growth models?",{"text":121,"@type":113},"Sulconazole reduces cancer cell proliferation and migration and suppresses their ability to mediate tumor growth in zebrafish embryos.","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},342419,1790213723,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"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":41},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","TYPE Original Research PUBLISHED 05 January 2024  \nDOI 10.3389/fimmu.2023.1278630  \nOPEN ACCESS  \nEDITED BY  \nTeresita Padilla-Benavides,  \nWesleyan University, United States  \nREVIEWED BY  \nQibin Liao,  \nShenzhen Third People’s Hospital, China Dalia Haydar,  \nChildren ’s National Hospital, United States  \n*CORRESPONDENCE  \nAbdel-Majid Khatib  \n [majid.khatib@inserm.fr](majid.khatib@inserm.fr)[ ](majid.khatib@inserm.fr)Geraldine Siegfried  \n geraldine.siegfried@inserm.fr  \n†PRESENT ADDRESS  \nMercedes Tome´,  \nGroup of Metabolism and Cell Signaling, Andalusian Molecular Biology and Regenerative Medicine Centre-CABIMERCSIC, Seville, Spain  \n‡These authors share first authorship  \nRECEIVED 16 August 2023  \nACCEPTED 30 November 2023  \nPUBLISHED 05 January 2024  \nCITATION  \nPernot S, Tome´ M, Galeano-Otero I, Evrard S, Badiola I, Delom F, Fessart D, Smani T, Siegfried G, Villoutreix BO and Khatib A-M (2024) Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-kB and calcium activity repression.  \nFront. Immunol. 14:1278630 .  \ndoi: 10.3389/fimmu.2023.1278630  \nCOPYRIGHT  \n© 2024 Pernot, Tome´ , Galeano-Otero, Evrard, Badiola, Delom, Fessart, Smani, Siegfried, Villoutreix and Khatib. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) .  \nThe 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.  \nSulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-kB and calcium activity repression  \nSimon Pernot 1,2‡, Mercedes Tom´e1†‡, Isabel Galeano-Otero 1, Serge Evrard 1,2, Iker Badiola 3, Frederic Delom 1,2,  \nDelphine Fessart 1,2, Tarik Smani 4, Geraldine Siegfried 1,2*, Bruno O. Villoutreix 5 and Abdel-Majid Khatib 1,2*  \n1 Reprograming tumor activitY and associaTed MicroenvironmEnt (Rytme), Bordeaux Institute of Oncology (BRIC)-UMR1312 Inserm, Universite´ of Bordeaux, Pessac, France, 2 Institut Bergonie´, Bordeaux, France, 3 Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain, 4Group of Cardiovascular Pathophysiology, Institute of Biomedicine of Seville, University Hospital of Virgen del Roco/ University of Seville/CSIC, Seville, Spain, 5 Integrative Computational Pharmacology and Data Mining, INSERM UMR 1141, Rob-ert-Debre´ Hospital, Paris, France  \nThe overexpression of the immunoinhibitory receptor programmed death-1 (PD1) on T-cells is involved in immune evasion in cancer. The use of anti-PD- 1/PDL-1 strategy has deeply changed the therapies of cancers and patient survival. However, their efficacy diverges greatly along with tumor type and patient populations. Thereby, novel treatments are needed to interfere with the anti-tumoral immune responses and propose an adjunct therapy. In the current study, we found that the antifungal drug Sulconazole (SCZ) inhibits PD-1 expression on activated PBMCs and T cells at the RNA and protein levels. SCZ repressed NF-kB and calcium signaling, both, involved in the induction of PD-1 . Further analysis revealed cancer cells treatment with SCZ inhibited their proliferation, and migration and ability to mediate tumor growth in zebrafish embryos . SCZ found also to inhibit calcium mobilization in cancer cells. These results suggest the SCZ therapeutic potential used alone or as adjunct strategy to prevent T-cell exhaustion and promotes cancer cell malignant phenotype repression in order to improve tumor eradication.  \nKEYWORDS  \nPD-1, Jurkat T cells, PBMCs, NF-kB, calcium, cancer, zebrafish  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nThe inhibitory receptor progr","cbCaiqCRjcrBhMTu","https://ap.wps.com/l/cbCaiqCRjcrBhMTu","pdf",5850996,12,"English","# Introduction\n## PD-1/PD-L1 pathway and cancer immune evasion\n## Limitations of anti-PD-1/PD-L1 therapies\n## Antifungal imidazole derivatives and sulconazole rationale","[{\"question\":\"What effect does sulconazole have on PD-1 expression in immune cells?\",\"answer\":\"Sulconazole inhibits PD-1 expression on activated PBMCs and T cells at both RNA and protein levels.\"},{\"question\":\"Which signaling pathways are repressed by sulconazole in relation to PD-1?\",\"answer\":\"Sulconazole represses NF-kB and calcium signaling, both involved in inducing PD-1.\"},{\"question\":\"How does sulconazole impact cancer cell behavior and tumor growth models?\",\"answer\":\"Sulconazole reduces cancer cell proliferation and migration and suppresses their ability to mediate tumor growth in zebrafish embryos.\"}]","Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-kB and calcium activity repression | PDF",1790046543]