{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:20:51Z","timestamp":1773307251833,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We describe an innovative approach for identification of tolerance breakage during immune checkpoint inhibitor therapy in malignant melanoma. Checkpoint inhibitor therapy enhances the immunologic clearance of cancer by suppressing pathways which induce immune suppression and tolerance. We posit that by analyzing temporal correlations of key markers of immune activation and tissue damage it would be possible to detect the onset of anticancer immune reaction as well as of immunologic adverse effects which might become crucial for optimization as well as safety of immune checkpoint inhibitor treatment. We analyzed time courses of routine laboratory values of serum tumor markers as well as of markers of immune activation in 17 patients with metastasized malignant melanoma receiving checkpoint inhibition and weekly laboratory controls. A parallel serum level increase of interleukin-6 and the tumor marker S100B could be identified in 13 patients, suggesting that the onset of tolerance breakage under checkpoint inhibition may be identified and measured. Immune-related adverse events in the patients were also accompanied by a peak of IL-6. In six patients, the onset of a putative anticancer immune reaction and the beginning of immunologic adverse events occurred in the same treatment cycle; in six patients the immunologic adverse reactions took place in separate cycles.<\/jats:p>","DOI":"10.3390\/ijms21062020","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T08:13:27Z","timestamp":1584519207000},"page":"2020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Correlative Monitoring of Immune Activation and Tissue Damage in Malignant Melanoma\u2014An Algorithm for Identification of Tolerance Breakage During Immune Checkpoint Inhibitor Therapy of Cancer"],"prefix":"10.3390","volume":"21","author":[{"given":"Renate U.","family":"Wahl","sequence":"first","affiliation":[{"name":"Department of Dermatology, Euregio Skin Cancer Center, RWTH Aachen University, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2911-1025","authenticated-orcid":false,"given":"Marike","family":"Leijs","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Euregio Skin Cancer Center, RWTH Aachen University, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"},{"name":"Department of Dermatology, Sint-Nikolaus Hospital, Hufengasse 4-8, 4700 Eupen, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"Araujo","sequence":"additional","affiliation":[{"name":"The AIWorks Research Lab, 7 Gower St, London WC1E 6HA, UK"},{"name":"Department of Computer Science, University College London, Malet Place, London WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-4754","authenticated-orcid":false,"given":"Albert","family":"R\u00fcbben","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Euregio Skin Cancer Center, RWTH Aachen University, Pauwelsstra\u00dfe 30, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. 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