{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:13:41Z","timestamp":1779196421992,"version":"3.51.4"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"13","funder":[{"name":"Else Kr\u00f6ner-Fresenius Stiftung","award":["Q-611.2354"],"award-info":[{"award-number":["Q-611.2354"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,12]]},"abstract":"<jats:p>\n                    Recent years have witnessed the groundbreaking success of immune checkpoint blockage (ICB) in metastasized malignant melanoma. However, biomarkers predicting the response to ICB are still urgently needed. In the present study, we investigated\n                    <jats:italic>CTLA4<\/jats:italic>\n                    promoter methylation (m\n                    <jats:italic>CTLA4<\/jats:italic>\n                    ) in 470 malignant melanoma patients from The Cancer Genome Atlas (non-ICB cohort) and in 50 individuals with metastasized malignant melanomas under PD-1\/CTLA-4\u2013targeted immunotherapy (ICB cohort). m\n                    <jats:italic>CTLA4<\/jats:italic>\n                    levels were quantified using the Infinium HumanMethylation450 BeadChip (non-ICB cohort) and methylation-specific quantitative real-time PCR in DNA formalin-fixed and paraffin-embedded tissues (ICB cohort). Methylation levels were associated with molecular and clinicopathological variables and analyzed with respect to response (irRECIST) and overall survival. CTLA-4 mRNA and m\n                    <jats:italic>CTLA4<\/jats:italic>\n                    showed a significant inverse correlation (non-ICB cohort: Spearman\u2019s\n                    <jats:italic>\u03c1<\/jats:italic>\n                    = \u20130.416,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). In ICB-treated melanoma patients, low m\n                    <jats:italic>CTLA4<\/jats:italic>\n                    was further strongly correlated with response to therapy (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.009, ANOVA) and overall survival (hazard ratio = 2.06 [95% CI: 1.29\u20133.29],\n                    <jats:italic>P<\/jats:italic>\n                    = 0.003). Our data strongly support the assumption that m\n                    <jats:italic>CTLA4<\/jats:italic>\n                    predicts response to both anti\u2013PD-1 and anti\u2013CTLA-4 targeted ICB in melanoma and provides paramount information for the selection of patients likely to respond to ICB.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.96793","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T11:01:22Z","timestamp":1531306882000},"source":"Crossref","is-referenced-by-count":77,"title":["CTLA4 methylation predicts response to anti\u2013PD-1 and anti\u2013CTLA-4 immunotherapy in melanoma patients"],"prefix":"10.1172","volume":"3","author":[{"given":"Diane","family":"Goltz","sequence":"first","affiliation":[{"name":"Institute of Pathology,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidrun","family":"Gevensleben","sequence":"additional","affiliation":[{"name":"Institute of 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