{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:15:26Z","timestamp":1789593326226,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors have transformed the treatment of advanced melanoma, yet many patients develop primary or acquired resistance. Although most work has focused on adaptive checkpoints (PD\u20101 and CTLA\u20104), accumulating evidence implicates innate immune suppression and stem\u2010like, drug\u2010resistant melanoma cell states. CD24, a small, heavily glycosylated glycosylphosphatidylinositol (GPI)\u2010anchored surface protein, sits at the intersection of these processes and is emerging as a context\u2010dependent biomarker and potential mediator of aggressive, therapy\u2010resistant melanoma states. In this review, we synthesize evidence indicating that CD24 is both a tumour\u2010intrinsic and tumour\u2010extrinsic regulator in melanoma. We summarize the structure, glycosylation and regulation of CD24, then discuss its role in melanoma, supporting phenotypic plasticity, sustaining stem\u2010like populations and promoting resistance to BRAF\u2010targeted and cytotoxic therapies through SOX2\/STAT3\u2010linked programmes. We then examine the CD24\u2013Siglec\u201010 axis as an innate immune checkpoint that suppresses macrophage and dendritic cell function, promotes immune\u2010excluded \u2018cold\u2019 tumour microenvironments and may shape responses to immunotherapy among CD24+ melanoma cells. We highlight CD24 in tumour tissue, blood and extracellular vesicles as potential biomarkers of prognosis and pathway activity, and review CD24\u2010axis interventions, including anti\u2010CD24 antibodies, Siglec\u201010 antagonists and CD24\u2010targeted CAR\u2010T\/CAR\u2010NK cells, with rational combinations alongside PD\u20101\/CTLA\u20104 blockade and MAPK\u2010targeted therapy. We propose that biomarker\u2010driven trials targeting this axis could open a new front in melanoma immunotherapy.<\/jats:p>","DOI":"10.1111\/exd.70271","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:35:31Z","timestamp":1778675731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>CD<\/scp>\n                    24 in Melanoma: Biomarker, Innate Immune Checkpoint and Emerging Therapeutic Target"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8815-8569","authenticated-orcid":false,"given":"Claudia","family":"Lasalle","sequence":"first","affiliation":[{"name":"Department of Dermatology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4963-6926","authenticated-orcid":false,"given":"Rachel C.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9796-7767","authenticated-orcid":false,"given":"Nicole C.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Dermatology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1701-6304","authenticated-orcid":false,"given":"Yulu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Giubellino","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2906-2454","authenticated-orcid":false,"given":"Kyle T.","family":"Amber","sequence":"additional","affiliation":[{"name":"Department of Dermatology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-0556","authenticated-orcid":false,"given":"Adrian P.","family":"Mansini","sequence":"additional","affiliation":[{"name":"Department of Dermatology Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Urology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2022.0160"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2407417"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30388-2"},{"key":"e_1_2_14_5_1","first-page":"42","article-title":"Exploring Resistance to Immune Checkpoint Inhibitors and Targeted Therapies in Melanoma","volume":"7","author":"Jalil A.","year":"2024","journal-title":"Cancer Drug Resistance"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042020-042741"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12081235"},{"issue":"11","key":"e_1_2_14_8_1","first-page":"4337","article-title":"CD24 Expression Predicts Poor Prognosis for Patients With Cutaneous Malignant Melanoma","volume":"7","author":"Tang M. R.","year":"2014","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168988"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S366625"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-023-03606-0"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0619"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.102598"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.216994"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01315-w"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015072"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1456-0"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1367959"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049865"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12610"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33249"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2009.119"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.09.006"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01222-y"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1846"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1055-9"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.10.139"},{"issue":"5","key":"e_1_2_14_28_1","first-page":"1149","article-title":"CD24 Overexpression in Cancer Development and Progression: A Meta\u2010Analysis","volume":"22","author":"Lee J. H.","year":"2009","journal-title":"Oncology Reports"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570163814666170818125036"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26718"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-025-02336-2"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6909"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S157043"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-23-0221"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.12.12.1241"},{"issue":"23","key":"e_1_2_14_36_1","first-page":"6714","article-title":"The CD24\/P\u2010Selectin Binding Pathway Initiates Lung Arrest of Human A125 Adenocarcinoma Cells1","volume":"60","author":"Friederichs J.","year":"2000","journal-title":"Cancer Research"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S196506"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23480"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17172828"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31609"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.329771.119"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12483"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.08.007"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6712"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3589"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00282"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.102152"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6391264"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2024.108613"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-024-01990-1"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.50"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10129-z"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-025-01165-3"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113456"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.01.010"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110557"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-007068"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.102"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25137252"},{"key":"e_1_2_14_60_1","volume-title":"Safety, Pharmacokinetics (PK), and Efficacy of ONC 841 in Advanced Solid Tumors","author":"ClinicalTrials.Gov","year":"2026"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2025.2557281"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202502758"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-44873-4"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12232750"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16880"},{"key":"e_1_2_14_66_1","volume-title":"A Study of IMM47 in Subjects With Advanced Solid Tumors","author":"ClinicalTrials.Gov","year":"2026"},{"key":"e_1_2_14_67_1","volume-title":"CD24Fc for the Treatment of Immune Related Adverse Events in Patients With Advanced Solid Tumors, TIRAEC Study","author":"Clinicaltrials.Gov","year":"2026"},{"key":"e_1_2_14_68_1","volume-title":"CD24Fc With Ipilimumab and Nivolumab to Decrease irAE (CINDI)","author":"ClinicalTrials.Gov","year":"2026"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116714"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.40"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2759-2"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.05.003"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.70271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/exd.70271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.70271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:05:29Z","timestamp":1780977929000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.70271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":71,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/exd.70271"],"URL":"https:\/\/doi.org\/10.1111\/exd.70271","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2026-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70271"}}