{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:11:14Z","timestamp":1790392274653,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["314061271"],"award-info":[{"award-number":["314061271"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Federal Ministry for Education and Research","award":["01EY1102"],"award-info":[{"award-number":["01EY1102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Treatment options for adrenocortical carcinoma (ACC), where mitotane remains a mainstay of therapy, are unsatisfactory. Response rates of ACC to immune checkpoint inhibition (ICI) are disappointing, and immune cells are scarce in ACC. Growth\/differentiation factor 15 (GDF-15) is a cytokine impairing tumoural immune infiltration. We here aimed to assess the value of serum GDF-15 for the prognosis of ACC and as a predictor of response to ICI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>GDF-15 was measured in serum samples of 151 patients and correlated with clinical data. Serum GDF-15 was analysed in a second cohort of 46 ACC patients who received ICI, including 14 responders. mRNA expression of GDF15 and genes related to immune response was quantified in 58 ACC tumour samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found GDF-15 induction in ACC cells and patients upon mitotane treatment. In ACC patients, serum GDF-15 concentration below the median was associated with significantly longer patient survival. GDF-15 levels in responders to ICI were significantly lower than in non-responders (P = .0379), and patients with low GDF-15 levels had a significant longer progression-free survival than patients with higher GDF-15 serum levels (P = .036). Expression of pro-inflammatory immune-related genes was lower in ACC tissue with GDF-15 expression above the median.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Mitotane increases GDF-15 levels and is associated with poor response to ICI. GDF-15 may mediate reduced infiltration with immune cells in ACC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf135","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T08:05:22Z","timestamp":1750838722000},"page":"146-155","source":"Crossref","is-referenced-by-count":4,"title":["Mitotane treatment of adrenocortical carcinoma induces tumoural secretion of GDF-15: impact on poor prognosis and impaired responsiveness to immunotherapy"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-8567","authenticated-orcid":false,"given":"Isabel","family":"Weigand","sequence":"first","affiliation":[{"name":"LMU University Hospital, Department of Medicine IV, Ludwig-Maximilians-University , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra S","family":"Triebig","sequence":"additional","affiliation":[{"name":"LMU University Hospital, Department of Medicine IV, Ludwig-Maximilians-University , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Maier","sequence":"additional","affiliation":[{"name":"LMU University Hospital, Department of Medicine IV, Ludwig-Maximilians-University , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Anderlik","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg , 97080 Wuerzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3499-5910","authenticated-orcid":false,"given":"Hanna","family":"Remde","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg , 97080 Wuerzburg 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,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4531-7568","authenticated-orcid":false,"given":"Miriam","family":"Reuter","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Wuerzburg , 97080 Wuerzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Schreiner","sequence":"additional","affiliation":[{"name":"LMU University Hospital, Department of Medicine IV, Ludwig-Maximilians-University , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Wedekink","sequence":"additional","affiliation":[{"name":"Experimental Tumour Immunology, Department of Obstetrics and Gynecology, University Hospital, University of Wuerzburg , 97080 Wuerzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-9231","authenticated-orcid":false,"given":"Oliver","family":"Scherf-Clavel","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy and Pharmacotherapy, Ludwig-Maximilians-University , 80337 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hoster","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University , 81337 Munich ,","place":["Germany"]},{"name":"Comprehensive Cancer Center Munich , 80336 Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4890-4450","authenticated-orcid":false,"given":"Kai C","family":"Wollert","sequence":"additional","affiliation":[{"name":"Division of Molecular and Translational Cardiology, Department of Cardiology and 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