{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:14:14Z","timestamp":1788146054109,"version":"build-2803163510"},"reference-count":116,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and S\u00e9zary syndrome (SS), is defined by malignant CD4+ T-cell clones that evolve within and remodel the skin and systemic immune compartments. For disease biology and immune remodeling, we prioritize evidence from human primary samples; for therapeutic implications, we integrate clinical-trial and translational biomarker studies. We organize evidence by compartment (skin vs. blood) and, within skin, by stage (patch\/plaque vs. tumor). Early patch\/plaque MF often shows features consistent with constrained inflammation: skin-resident memory T-cell (TRM)-like malignant clones are in a Th1-leaning microenvironment with relatively preserved cytotoxic surveillance. Progression to tumor-stage MF (and\/or large-cell transformation) is frequently associated with clonal dominance, Th2 cytokine polarization, upregulation of checkpoint pathways, and remodeling of myeloid\/fibroblast populations. SS is typically associated with leukemic clonal dominance, systemic Th2 skewing, and broad impairment of cytotoxic immune control. These trajectories support an interpretive framework that aligns immune-directed therapies with compartment- and stage-associated biology; these include strategies that (i) deplete malignant clones (e.g., CCR4, CD30, KIR3DL2 targeting), (ii) re-engage exhausted effectors (PD-1\/PD-L1 axis), (iii) reprogram cytokine balance (IFN-\u03b3, IL-12, extracorporeal photopheresis), or (iv) suppress malignant signaling programs with secondary immune effects (JAK\/STAT inhibition). We highlight potential candidate predictive biomarkers at varying levels of maturity, most of which require prospective validation, including antigen density, compartmental tumor burden, tumor cell fraction, effector-cell substrate, and interferon\/cytokine signatures.<\/jats:p>","DOI":"10.3390\/cells15171576","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Dysregulation, Compartment-Specific Biology, and Therapeutic Biomarkers in Mycosis Fungoides and S\u00e9zary Syndrome"],"prefix":"10.3390","volume":"15","author":[{"given":"Tiantian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Central Florida\/HCA, Pensacola, FL 32514, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simo","family":"Du","sequence":"additional","affiliation":[{"name":"Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Flushing Hospital Medical Center, Flushing, NY 11355, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.path.2014.02.006","article-title":"CD30-Negative Cutaneous T-Cell Lymphomas Other than Mycosis Fungoides","volume":"7","author":"Willemze","year":"2014","journal-title":"Surg. 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