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The immunopathology of MF and SS is complex, but recent advances in tumor microenvironment understanding have identified CCR4 as a promising therapeutic target. CCR4 is widely expressed on malignant T cells and Tregs in the skin and peripheral blood of patients with MF and SS. The interaction of CCR4 with its dominant ligands CCL17 and CCL22 plays a critical role in the development and progression of CTCL, facilitating the movement into, and accumulation of, CCR4\u2010expressing T cells in the skin, and recruiting CCR4\u2010expressing Tregs into the tumor microenvironment. Expression of CCR4 is upregulated at all stages of MF and in SS, increasing with advancing disease. Several CCR4\u2010targeted therapies are being evaluated, including \u201cchemotoxins\u201d targeting CCR4 via CCL17, CCR4\u2010directed chimeric antigen receptor\u2010modified T\u2010cell therapies, small\u2010molecule CCR4 antagonists, and anti\u2010CCR4 monoclonal antibodies. Only one is currently approved: mogamulizumab, a defucosylated, fully humanized, anti\u2010CCR4, monoclonal antibody for the treatment of relapsed\/refractory MF and SS. Clinical trial da1ta confirm that mogamulizumab is an effective and well\u2010tolerated treatment for relapsed\/refractory MF or SS, demonstrating the clinical value of targeting CCR4.<\/jats:p>","DOI":"10.1002\/eji.202049043","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T06:14:40Z","timestamp":1617430480000},"page":"1660-1671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["CCR4 in cutaneous T\u2010cell lymphoma: Therapeutic targeting of a pathogenic driver"],"prefix":"10.1002","volume":"51","author":[{"given":"Jan P.","family":"Nicolay","sequence":"first","affiliation":[{"name":"Department of Dermatology University Medical Centre Mannheim University of Heidelberg  Mannheim Germany"},{"name":"Skin Cancer Unit German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Section of Clinical and Experimental Dermatology Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana D.","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Medical Centre Mannheim University of Heidelberg  Mannheim Germany"},{"name":"Skin Cancer Unit German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Section of Clinical and Experimental Dermatology Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Alberti\u2010Violetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Interna UOC Dermatologia IRCCS Ca' Granda Foundation\u2013Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Berti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Interna UOC Dermatologia IRCCS Ca' Granda Foundation\u2013Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-054601"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24826"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-016-0594-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21888"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.356"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21738"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.02.027"},{"key":"e_1_2_8_9_1","unstructured":"National Comprehensive Cancer Network (NCCN).(2019). 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