Evolving Insights in the Pathogenesis and Therapy of Cutaneous T‐cell lymphoma (Mycosis Fungoides and Sezary Syndrome)

Abstract

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies derived from skin-homing T cells. The most common forms of CTCL are Mycosis Fungoides (MF) and Sezary Syndrome (SS). Accurate diagnosis remains a challenge due to the heterogeneity of presentation and the lack of highly characteristic immunophenotypical and genetic markers. Over the past decade molecular studies have improved our understanding of the biology of CTCL. The identification of gene expression differences between normal and malignant T-cells has led to promising new diagnostic and prognostic biomarkers that now need validation to be incorporated into clinical practice. These biomarkers may also provide insight into the mechanism of development of CTCL. Additionally, treatment options have expanded with the approval of new agents, such as histone deacetylase inhibitors. A better understanding of the cell biology, immunology and genetics underlying the development and progression of CTCL will allow the design of more rational treatment strategies for these malignancies. This review summarizes the clinical epidemiology, staging and natural history of MF and SS; discusses the immunopathogenesis of MF and the functional role of the malignant T-cells; and reviews the latest advances in MF and SS treatment.

PLCG1 mutations in cutaneous T-cell lymphomas

“…[10][11][12] Early stages of CTCL are treated with combinations of UV and immunotherapy, with mono-or polychemotherapy being reserved for cases that do not respond to previous treatment. New therapies based on monoclonal antibodies (including CD25, CD4, CD30, CD3, and CCR4) are being explored, as are other therapeutic agents directed against epigenetic targets (eg, histone deacetylases inhibitors) or proteasome inhibitors such as bortezomib (for a review, see Wong et al 13 ), but to date, aggressive forms of CTCL, including SS and tumoral MF, lack effective targeted therapy.…”

Highly cytotoxic natural killer cells are associated with poor prognosis in patients with cutaneous T-cell lymphoma

“…There are two main subtypes of CTCL: an indolent form termed mycosis fungoides (MF), which is largely limited to the skin, and Sézary syndrome (SS), an aggressive leukemic variant of the disease which can manifest systemically. [1][2][3] Previous studies have demonstrated defects in cell-mediated immunity in CTCL patients, including altered cytokine profiles and impaired neutrophil function, which lead to a high incidence of recurrent bacterial and viral infections as a result of decreased Th1-mediated immunity. [4][5][6][7][8][9] It has also been reported that natural killer (NK)-cell function is decreased in CTCL patients, [10][11][12][13][14] which could contribute to an overall decrease in the innate immune response to both neoplastic cells and viral or bacterial pathogens.…”

Deficient Cutaneous Antibacterial Competence in Cutaneous T-Cell Lymphomas: Role of Th2-Mediated Biased Th17 Function

“…Mycosis fungoides and S ezary syndrome are two common CTCL forms, accounting for approximately 67% of cases. For the United States, their incidence has been estimated to be approximately 3 to 8 cases per million inhabitants per year (1)(2)(3). Affected individuals are mostly older than 50 years.…”