{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:13:29Z","timestamp":1779196409893,"version":"3.51.4"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"name":"Cancer Research Institute","award":["Clinic"],"award-info":[{"award-number":["Clinic"]}]},{"name":"Cancer Research Institute","award":["Laboratory Integration Program (CLIP) grant"],"award-info":[{"award-number":["Laboratory Integration Program (CLIP) grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,6]]},"abstract":"<jats:p>Organ transplant recipients (OTRs) on cyclosporine A (CSA) are prone to catastrophic cutaneous squamous cell carcinoma (SCC). Allograft-sparing, cancer-targeting systemic treatments are unavailable. We have shown increased risk for catastrophic SCC in OTRs via CSA-mediated induction of IL-22. Herein, we found that CSA drives SCC proliferation and tumor growth through IL-22 and JAK\/STAT pathway induction. We in turn inhibited SCC growth with an FDA-approved JAK1\/2 inhibitor, ruxolitinib. In human SCC cells, the greatest proliferative response to IL-22 and CSA treatment occurred in nonmetastasizing lines. IL-22 treatment upregulated JAK1 and STAT1\/3 in A431 SCC cells. JAK\/STAT pathway genes were highly expressed in tumors from a cohort of CSA-exposed OTRs and in SCC with high risk for metastasis. Compared with immunocompetent SCC, genes associated with innate immunity, response to DNA damage, and p53 regulation were differentially expressed in SCC from OTRs. In nude mice engrafted with human A431 cells, IL-22 and CSA treatment increased tumor growth and upregulated IL-22 receptor, JAK1, and STAT1\/3 expression. Ruxolitinib treatment significantly reduced tumor volume and reversed the accelerated tumor growth. CSA and IL-22 exacerbate aggressive behavior in SCC. Targeting the IL-22 axis via selective JAK\/STAT inhibition may reduce the progression of aggressive SCC in OTRs, without compromising immunosuppression.<\/jats:p>","DOI":"10.1172\/jci.insight.120750","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T11:02:36Z","timestamp":1536145356000},"source":"Crossref","is-referenced-by-count":30,"title":["Ruxolitinib inhibits cyclosporine-induced proliferation of cutaneous squamous cell carcinoma"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3898-6824","authenticated-orcid":true,"given":"Melody","family":"Abikhair Burgo","sequence":"first","affiliation":[{"name":"Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazanin","family":"Roudiani","sequence":"additional","affiliation":[{"name":"Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Pediatric Urology, Department of Urology, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis L.","family":"Santana","sequence":"additional","affiliation":[{"name":"Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Doudican","sequence":"additional","affiliation":[{"name":"Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Proby","sequence":"additional","affiliation":[{"name":"Division of Cancer Research, Jacqui Wood Cancer Centre, University of Dundee, Dundee, Scotland, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1190-9626","authenticated-orcid":true,"given":"Diane","family":"Felsen","sequence":"additional","affiliation":[{"name":"Institute for Pediatric Urology, Department of Urology, Weill Cornell Medicine, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Carucci","sequence":"additional","affiliation":[{"name":"Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2018,9,6]]},"reference":[{"key":"B1"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2014.08.036"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2016.07.003"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2016.5118"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3064"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.1912"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2016.4920"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022137"},{"issue":"2","key":"B9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.det.2011.02.004","article-title":"Management of skin cancer in solid-organ transplant recipients: a multidisciplinary approach","volume":"29","author":"Greenberg","year":"2011","journal-title":"Dermatol Clin"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14382"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14153"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2005.07021.x"},{"key":"B13"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.01.004"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2009.10.001"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23858.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2014.02.039"},{"issue":"8","key":"B18","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.86434","article-title":"Cyclosporine A immunosuppression drives catastrophic squamous cell carcinoma through IL-22","volume":"1","author":"Abikhair","year":"2016","journal-title":"JCI Insight"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062154"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911472106"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2014.04.005"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4176"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747183"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13660"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03539.x"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13073"},{"key":"B27"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.150"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.06.001"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2012.06.316"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0156"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.4578"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.08.140"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-484642"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.5326"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13593"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw937"},{"key":"B38","doi-asserted-by":"crossref","DOI":"10.1038\/srep24006","article-title":"CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity","volume":"6","author":"Vallath","year":"2016","journal-title":"Sci Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.139.3.301"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1509268"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdcr.2017.06.005"},{"key":"B43","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms12493","article-title":"Inactivation of TGF\u03b2 receptors in stem cells drives cutaneous squamous cell carcinoma","volume":"7","author":"Cammareri","year":"2016","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.226"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.11.011"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nature08996"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.06.007"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.11.004"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2009.03324.x"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nm1720"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.024"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29450"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006101143"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04269.x"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.538"},{"issue":"2","key":"B56","first-page":"474","article-title":"Treg cells: a potential regulator for IL-22 expression?","volume":"7","author":"Lin","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.01.035"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.296"},{"issue":"3","key":"B59","first-page":"S19","article-title":"Ruxolitinib prevents cytokine release syndrome after car T-cell therapy without impairing the anti-tumor effect in a xenograft model","volume":"23","author":"Kenderian","year":"2017","journal-title":"Blood"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2016.12.005"},{"key":"B61","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/283617","article-title":"JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis","volume":"2014","author":"Hsu","year":"2014","journal-title":"J Immunol Res"},{"issue":"5","key":"B62","first-page":"508","article-title":"Aggressive skin cancers occurring in patients treated with the janus kinase inhibitor ruxolitinib","volume":"16","author":"Blechman","year":"2017","journal-title":"J Drugs Dermatol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.148"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12588"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000000798"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-457531"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2000.009002104.x"},{"issue":"5","key":"B68","first-page":"1657","article-title":"Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas","volume":"41","author":"Rheinwald","year":"1981","journal-title":"Cancer Res"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.180"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.10.036"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700157"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/120750\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:42:28Z","timestamp":1779194548000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/120750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,6]]},"references-count":72,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2018,9,6]]},"published-print":{"date-parts":[[2018,9,6]]}},"alternative-id":["10.1172\/jci.insight.120750"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.120750","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,6]]},"article-number":"e120750"}}