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Bulk RNA sequencing analysis revealed elevated expression of\n                    <jats:italic>Klotho<\/jats:italic>\n                    (\n                    <jats:italic>Kl<\/jats:italic>\n                    ) in gliomas derived from irradiated glioma\u2010bearing mice.\n                    <jats:italic>Klotho<\/jats:italic>\n                    , which encodes an anti\u2010aging protein, was found to be upregulated in glioma\u2010associated microglia\/macrophages (GAMs) exhibiting an M1 pro\u2010inflammatory phenotype. This upregulation appeared to enhance the antitumor efficacy of a combination of radiotherapy and dendritic cell (DC) immunotherapy. Furthermore, transcript levels of\n                    <jats:italic>KL<\/jats:italic>\n                    in tumor specimens and corresponding serum levels in glioblastoma patients undergoing DC immunotherapy were correlated with favorable prognostic outcomes and improved treatment responses. Given its expression in human M1\u2010like GAMs, serum KL levels can offer valuable insights into the immune microenvironment and hold clinical significance as a peripheral biomarker. These findings highlight the pivotal role of Klotho as a prognostic biomarker for predicting responses to immunotherapy, with potential applications for monitoring tumor progression or regression through changes in serum levels.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70038","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:24:20Z","timestamp":1753093460000},"page":"2156-2172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The anti\u2010aging Klotho protects glioblastoma macrophages from radiotherapy\u2010induced inflammation and predicts immunotherapy response"],"prefix":"10.1002","volume":"157","author":[{"given":"Andrea","family":"Galluzzo","sequence":"first","affiliation":[{"name":"Unit of Immunotherapy of Brain Tumors Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"},{"name":"Unit of Neuroncology Fondazione IRCCS Istituto Neurologico Carlo 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