{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:31:44Z","timestamp":1787671904265,"version":"build-2736575974"},"reference-count":95,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"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":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>S\u00e9zary syndrome (SS) and leukaemic mycosis fungoides (MF) are aggressive cutaneous T\u2010cell lymphomas (CTCLs) with poor prognosis and limited treatment options. Single\u2010cell RNA sequencing (scRNA\u2010seq) offers an opportunity to dissect malignant heterogeneity and immune dysregulation yet has been underutilized in leukaemic CTCL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To define transcriptional heterogeneity within malignant T cells, identify immunomodulatory signals shaping the tumour microenvironment and uncover actionable vulnerabilities in SS and leukaemic MF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed 144,321 peripheral blood mononuclear cells from 22 patients (SS or leukaemic MF) and 7 healthy controls using scRNA\u2010seq, with CITE\u2010seq and TCR\u2010seq in subsets. Public and prospectively collected datasets were integrated after rigorous per\u2010sample quality control, batch correction and malignancy assignment. Differential gene expression and cell\u2013cell communication analyses were performed using complementary modelling approaches with correction for sparsity and multiple testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three transcriptionally distinct malignant T\u2010cell (MTC) subtypes were identified: central memory\u2010like (MTC CM), effector\/effector memory\u2010like (MTC E\/EM) and regulatory\u2010like (MTC Reg), each with unique expression programmes and putative vulnerabilities. MTC CM, the dominant population, expressed central memory markers, Th2\/Th22 skewing and a broader KIR repertoire (\n                      <jats:italic>KIR3DL2, KIR3DL1, KIR2DL3<\/jats:italic>\n                      ) than previously reported. MTC E\/EM and MTC Reg were enriched for\n                      <jats:italic>NR4A1<\/jats:italic>\n                      and\n                      <jats:italic>ITGB1<\/jats:italic>\n                      , respectively. Cell\u2013cell communication analysis revealed KIR\u2013MHC\u2010I signalling and suggested that MTC\u2010derived TNF and IL\u201010 may drive JAK\/STAT pathway activity in non\u2010T cells, indicating an underrecognized dimension of tumour\u2010induced immune reprogramming.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is one of the most comprehensive single\u2010cell studies of leukaemic CTCL to date. We uncover new malignant T\u2010cell states, broaden the known repertoire of KIR expression, and propose mechanisms of immune evasion that may contribute to treatment resistance. These findings lay the groundwork for subtype\u2010specific and microenvironment\u2010informed therapeutic strategies in S\u00e9zary syndrome, with potential implications for guiding targeted therapy selection but require validation in larger, independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdv.70368","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:24:39Z","timestamp":1772983479000},"page":"1535-1549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mapping malignant T\u2010cell states and immune circuits in S\u00e9zary syndrome by single\u2010cell analysis"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-8890","authenticated-orcid":false,"given":"Beth A.","family":"Childs","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology UT Southwestern  Dallas Texas USA"},{"name":"Department 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