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In the CTCL microenvironment, cell interactions mediated by cell signaling pathways are altered. Defining changes in cell signaling enables to understand T\u2010cell deregulations in the CTCL microenvironment and thus the progression of the disease. Moreover, characterizing signaling networks activated in CTCL stages can lead to consider new molecular biomarkers and therapeutic targets. Focusing on mycosis fungoides (MF), the most frequent variant of CTCL, and S\u00e9zary syndrome (SS), its leukemic variant, this review highlights recent molecular and genetic findings revealing modifications of key signaling pathways involved in (1) cell proliferation, cell growth, and cell survival such as MAP kinases and PI3K\/Akt; (2) immune responses derived from TCR, TLR, JAK\/STAT, and NF\u2010kB; and (3) changes in tissue conditions such as extracellular matrix remodeling, hypoxia, and angiogenesis. Alterations in these signaling networks promote malignant T\u2010cell proliferation and survival, T\u2010cell migration, inflammation, and suppression of immune regulation of malignant T cells, making a skin microenvironment that allows disease progression. Targeting key proteins of these signaling pathways, using molecules already available and used in research, in clinical trials, and with other disease indications, can open the way to different therapeutic options in CTCL treatment.<\/jats:p>","DOI":"10.1111\/ijd.15451","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T07:47:27Z","timestamp":1617954447000},"page":"1462-1480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cell signaling in cutaneous T\u2010cell lymphoma microenvironment: promising targets for molecular\u2010specific treatment"],"prefix":"10.1111","volume":"60","author":[{"given":"Natalia","family":"Rend\u00f3n\u2010Serna","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda Universidad de Antioquia Medellin Colombia"},{"name":"Centro de Investigaciones Dermatol\u00f3gicas CIDERM Facultad de Medicina Universidad De Antioquia Medellin Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis A.","family":"Correa\u2010Londo\u00f1o","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Dermatol\u00f3gicas CIDERM Facultad de Medicina Universidad De Antioquia Medellin Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita M.","family":"Vel\u00e1squez\u2010Lopera","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Dermatol\u00f3gicas CIDERM Facultad de Medicina Universidad De Antioquia Medellin Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9963-6583","authenticated-orcid":false,"given":"Maria","family":"Bermudez\u2010Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Universidad de Antioquia Medellin Colombia"},{"name":"Centro de Investigaciones Dermatol\u00f3gicas CIDERM Facultad de Medicina Universidad De Antioquia Medellin Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2016.07.010"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.02.027"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60420-1"},{"issue":"4","key":"e_1_2_9_5_1","first-page":"205","article-title":"Diagn\u00f3stico y manejo del linfoma cut\u00e1neo de c\u00e9lulas T de tipo micosis fungoides y s\u00edndrome de S\u00e8zary","volume":"18","author":"Valencia OJ","year":"2010","journal-title":"Rev Asoc Colomb Dermatol"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8829.1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-016-0351-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/ddg.12900","article-title":"S\u00e9zary syndrome: old enigmas, new targets","volume":"14","author":"Nicolay JP","year":"2016","journal-title":"J Dtsch Dermatol Ges"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3356"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3442"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.04.027"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5325-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.2007.00924.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.223"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12547"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3370"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029541"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-02-768234"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2002.1986"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847655"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1211040"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4558"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190410001693560"},{"key":"e_1_2_9_24_1","first-page":"402","article-title":"Linfoma cut\u00e1neo de c\u00e9lulas T. 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