Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma

J Invest Dermatol. 2018 May;138(5):1116-1125. doi: 10.1016/j.jid.2017.10.028. Epub 2017 Nov 8.


Cutaneous T-cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic, and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome showed a highly heterogeneous landscape of genetic perturbations, and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway previously implicated in cutaneous T-cell lymphoma pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of cutaneous T-cell lymphoma. Using this mouse model, we show that T-cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / physiology*
  • DNA Copy Number Variations
  • Disease Models, Animal
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lymphoma, T-Cell, Cutaneous / etiology*
  • Lymphoma, T-Cell, Cutaneous / genetics
  • Lymphoma, T-Cell, Cutaneous / immunology
  • Mice
  • Microbiota
  • Receptors, Antigen, T-Cell / physiology
  • STAT3 Transcription Factor / physiology
  • Sezary Syndrome / genetics
  • Signal Transduction / physiology*
  • Skin Neoplasms / etiology*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology


  • Cytokines
  • Receptors, Antigen, T-Cell
  • STAT3 Transcription Factor