Journal Article (Review Article)

DKFZ-2026-01955

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cellular and molecular aberrations generating new immunotherapeutic approaches in mycosis fungoides and Sézary syndrome: a comprehensive review of literature.

Flechtenmacher, A. S. ; Melchers, S.DKFZ* ; Nicolay, J. (Last author)DKFZ*

2026
Frontiers Media Lausanne

Abstract: Recent advances in molecular and immunologic profiling have substantially refined the understanding of mycosis fungoides (MF) and Sézary syndrome (SS), the two most prominent subtypes of cutaneous T-cell lymphomas (CTCL). CTCL comprise a heterogeneous group of lymphoid malignancies characterized by clonal proliferation of malignant T-cell with cutaneous tropism. The pathogenesis of MF and SS appears to be driven by convergent oncogenic programs involving dysregulated JAK/STAT, NF-κB, PI3K/AKT/mTOR, and MAPK signaling, epigenetic reprogramming, apoptosis resistance, immune escape, and microenvironmental support. In parallel, altered surface phenotypes and chemokine receptor programs shape tissue tropism across skin, blood, and lymph nodes, while the tumor microenvironment promotes tumor persistence and Th2-skewed immune polarization. These insights have translated into novel targeted and immune-based therapies. This review summarizes current insights into the cell-intrinsic and microenvironmental biology of MF and SS and discusses emerging approaches aimed at achieving more durable and personalized disease control.

Keyword(s): Humans (MeSH) ; Sezary Syndrome: therapy (MeSH) ; Sezary Syndrome: immunology (MeSH) ; Sezary Syndrome: genetics (MeSH) ; Sezary Syndrome: pathology (MeSH) ; Sezary Syndrome: etiology (MeSH) ; Mycosis Fungoides: therapy (MeSH) ; Mycosis Fungoides: immunology (MeSH) ; Mycosis Fungoides: genetics (MeSH) ; Mycosis Fungoides: pathology (MeSH) ; Mycosis Fungoides: etiology (MeSH) ; Tumor Microenvironment: immunology (MeSH) ; Immunotherapy: methods (MeSH) ; Skin Neoplasms: immunology (MeSH) ; Skin Neoplasms: therapy (MeSH) ; Skin Neoplasms: genetics (MeSH) ; Animals (MeSH) ; Signal Transduction (MeSH) ; CTCL (cutaneous T-cell lymphoma) ; Sezary syndrome ; antibody-drug conjugate (ADC) ; chimeric antigen receptor (CAR T) ; immunotherapy ; molecular target ; mycosis fundgoides ; tumor microenvironment - TME

Note: #LA:A370#

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Contributing Institute(s):

1. KKE Dermatoonkologie (A370)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2026

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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