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Molecular pathogenesis of Cutaneous T cell Lymphoma: Role of chemokines, cytokines, and dysregulated signaling pathways

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journal contribution
submitted on 2023-10-16, 07:54 and posted on 2023-10-17, 04:52 authored by Kalyani Patil, Shilpa Kuttikrishnan, Abdul Q. Khan, Fareed Ahmad, Majid Alam, Joerg Buddenkotte, Aamir Ahmad, Martin Steinhoff, Shahab Uddin

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of lymphoproliferative neoplasms that exhibit a wide spectrum of immune-phenotypical, clinical, and histopathological features. The biology of CTCL is complex and remains elusive. In recent years, the application of next-generation sequencing (NGS) has evolved our understanding of the pathogenetic mechanisms, including genetic aberrations and epigenetic abnormalities that shape the mutational landscape of CTCL and represent one of the important pro-tumorigenic principles in CTCL initiation and progression. Still, identification of the major pathophysiological pathways including genetic and epigenetic components that mediate malignant clonal T cell expansion has not been achieved. This is of prime importance given the role of malignant T cell clones in fostering T helper 2 (Th2)-bias tumor microenvironment and fueling progressive immune dysregulation and tumor cell growth in CTCL patients, manifested by the secretion of Th2-associated cytokines and chemokines. Alterations in malignant cytokine and chemokine expression patterns orchestrate the inflammatory milieu and influence the migration dynamics of malignant clonal T cells. Here, we highlight recent insights about the molecular mechanisms of CTCL pathogenesis, emphasizing the role of cytokines, chemokines, and associated downstream signaling networks in driving immune defects, malignant transformation, and disease progression. In-depth characterization of the CTCL immunophenotype and tumoral microenvironment offers a facile opportunity to expand the therapeutic armamentarium of CTCL, an intractable malignant skin disease with poor prognosis and in dire need of curative treatment approaches.

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Published in: Seminars in Cancer Biology
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Open Access funding provided by the Qatar National Library



  • English



Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License

Institution affiliated with

  • Hamad Medical Corporation
  • Academic Health System - HMC
  • Interim Translational Research Institute - HMC
  • Dermatology Institute - HMC
  • Rumailah Hospital - HMC
  • Weill Cornell Medicine - Qatar
  • Qatar University
  • Laboratory Animal Research Center - QU