{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:26:28Z","timestamp":1787725588722,"version":"build-2784847793"},"reference-count":12,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cytokine\u2010induced killer (CIK) cell therapy has proven successful in clinical trials regarding glioblastoma. Equally important are the hints suggesting peroxisome proliferator\u2010activated receptors (PPARs) ligands being co\u2010expressed in the central nervous system (CNS). This provides a rationale about investigating the possible synergistic effect of CIK cells and PPARs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>We investigated neuroblastoma and glioblastoma cell lines with mature CIK cells and the PPAR\u03b3 antagonist GW\u20109662 to assess the effects on cell viability, candidate gene expression (Wnt\/\u03b2\u2010catenin signalling, DNMT1) and global methylation levels (5\u2010methylcytosine, LINE\u20101).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using a clinical applicable PPAR\u2010\u03b3\u2009inhibitor, we showed that (1) PPAR\u03b3\u2010antagonist GW\u20109662 suppressed tumor cell growth in both neuroblastoma and glioblastoma cells, (2) PPAR\u03b3\u2009inhibition had restricted effect on the expression of Wnt\/\u03b2\u2010catenin associated genes, (3) inhibition of PPAR\u03b3\u2009led to downregulation of DNMT1 expression, supporting their hypothesized interaction in cancer, (4) a partial modulation of global LINE\u20101 methylation levels was observed, indicating their role in epigenetic processes, and (5) Combining PPAR\u03b3\u2009inhibition with CIK cell immunotherapy enhanced cell lysis significantly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We provide evidence that PPAR ligands in combination with CIK cell immunotherapy could be a valuable option for malignant CNS tumors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70497","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T11:40:15Z","timestamp":1734349215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Balancing CIK Cell Cancer Immunotherapy and PPAR Ligands: One Potential Therapeutic Application for CNS Malignancies"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9042-6698","authenticated-orcid":false,"given":"Kira","family":"Vordermark","sequence":"first","affiliation":[{"name":"Department of Integrated Oncology, Center for Integrated Oncology (CIO) University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JingJing","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Integrated Oncology, Center for Integrated Oncology (CIO) University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2216-5389","authenticated-orcid":false,"given":"Amit","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Integrated Oncology, Center for Integrated Oncology (CIO) University Hospital of Bonn  Bonn Germany"},{"name":"Department of Stereotactic and Functional Neurosurgery University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarek","family":"Maciacyzk","sequence":"additional","affiliation":[{"name":"Department of Stereotactic and Functional Neurosurgery University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo G. H.","family":"Schmidt\u2010Wolf","sequence":"additional","affiliation":[{"name":"Department of Integrated Oncology, Center for Integrated Oncology (CIO) University Hospital of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010021\u201002184\u20102"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.851628"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262\u2010023\u201003605\u20101"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3038164"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2014.00052"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.02.036"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.063438"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060\u2010010\u20100185\u2010x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010018\u20102791\u20105"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00090"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14133165"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13163993"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.70497","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T08:56:18Z","timestamp":1738918578000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.70497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":12,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/cam4.70497"],"URL":"https:\/\/doi.org\/10.1002\/cam4.70497","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70497"}}