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Despite advances, the mechanisms underlying disease progression\u2014from early patch and plaque lesions to advanced tumor stages\u2014remain incompletely understood. Chemokines and their receptors play crucial roles in the migration and survival of malignant T cells, influencing tissue invasion, immune evasion, and dissemination. This review highlights the altered expression of chemokine receptors like CCR4, CCR7, CCR8, CCR10, CXCR3, and CXCR4 in MF\/SS and their contribution to disease evolution. It also explores the transition from a Th1 to a Th2 immune profile, linked to tumor progression. The dual role of chemokines in physiology and pathology is examined, with emphasis on their therapeutic potential in CTCL.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1646669","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:25:46Z","timestamp":1754630746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Unraveling the role of chemokines in cutaneous T-cell lymphoma: expression levels at different stages"],"prefix":"10.3389","volume":"16","author":[{"given":"Alba","family":"Guglielmo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado","family":"Zengarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Tugnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Zinzani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Borghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Corazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelangelo","family":"La Placa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Maria","family":"Piraccini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Pileri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the world health organization classification of haematolymphoid tumours: lymphoid neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.89","article-title":"Upregulation of inflammatory cytokines and oncogenic signal pathways preceding tumor formation in a murine model of T-cell lymphoma in skin","volume":"131","author":"Wu","year":"2011","journal-title":"J Invest Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12555.x","article-title":"Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides","volume":"121","author":"Kallinich","year":"2003","journal-title":"J Invest Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-12-243","article-title":"The chemokine and chemokine receptor superfamilies and their molecular evolution","volume":"7","author":"Zlotnik","year":"2006","journal-title":"Genome Biol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1146\/annurev-immunol-032713-120145","article-title":"Chemokines and chemokine receptors: positioning cells for host defense and immunity","volume":"32","author":"Griffith","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-014-0313-y","article-title":"Chemokines and skin diseases","volume":"63","author":"Sugaya","year":"2015","journal-title":"Arch Immunol Ther Exp"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2010.05.005","article-title":"Chemokines and cutaneous lymphoma","volume":"59","author":"Sugaya","year":"2010","journal-title":"J Dermatol Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102780","article-title":"The microenvironment\u2019s role in mycosis fungoides and s\u00e9zary syndrome: from progression to therapeutic implications","volume":"10","author":"Pileri","year":"2021","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.07.026","article-title":"Phenotypical markers, molecular mutations, and immune microenvironment as targets for new treatments in patients with mycosis fungoides and\/or s\u00e9zary syndrome","volume":"141","author":"Quaglino","year":"2021","journal-title":"J Invest Dermatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cells13070584","article-title":"The role of cytokines in cutaneous T cell lymphoma: A focus on the state of the art and possible therapeutic targets","volume":"13","author":"Guglielmo","year":"2024","journal-title":"Cells"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/1744666X.2025.2507332","article-title":"Borghi,Alessandro, Schettini,Natale, Perillo,Marcello, Corazza,Monica, Piraccini,Bianca Maria, and Pileri A. 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