Malignant and Benign T Cells Constituting Cutaneous T-Cell Lymphoma

Abstract

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, including various clinical manifestations, such as mycosis fungoides (MF) and Sézary syndrome (SS). CTCL mostly develops from CD4 T cells with the skin-tropic memory phenotype. Malignant T cells in MF lesions show the phenotype of skin resident memory T cells (TRM), which reside in the peripheral tissues for long periods and do not recirculate. On the other hand, malignant T cells in SS represent the phenotype of central memory T cells (TCM), which are characterized by recirculation to and from the blood and lymphoid tissues. The kinetics and the functional characteristics of malignant cells in CTCL are still unclear due, in part, to the fact that both the malignant cells and the T cells exerting anti-tumor activity possess the same characteristics as T cells. Capturing the features of both the malignant and the benign T cells is necessary for understanding the pathogenesis of CTCL and would lead to new therapeutic strategies specifically targeting the skin malignant T cells or benign T cells.

What Does the Future Hold for Biomarkers of Response to Extracorporeal Photopheresis for Mycosis Fungoides and Sézary Syndrome?

“…MF and SzS cell phenotypes exhibit significant heterogeneity [ 6 , 7 ], and although MF cells typically exhibit a TEM phenotype and are confined to the skin while SzS cells typically exhibit a TCM phenotype and move through the peripheral blood, skin, and lymph nodes, a recent study found no correlation between disease and the phenotype of the cell of origin [ 4 , 5 , 17 ]. Further, studies have shown characteristic ultraviolet (UV) light-associated mutations in both MF and SzS cells, suggesting that these cells acquire mutations in the skin before clonal proliferation [ 17 ].…”

“…In contrast, SzS cells frequently have central memory T cells (TCM) phenotype [ 4 ]. Those differences were thought to account for the distinctions in the behavior and progression of MF and SzS [ 5 ]. However, recent studies have shown that the corresponding markers of malignant T cells may change during the course of the disease, not only between patients who carry the same diagnosis, but also with some level of heterogeneity within the same patient [ 6 , 7 ].…”

Spatially Guided and Single Cell Tools to Map the Microenvironment in Cutaneous T-Cell Lymphoma

“…Changes in the frequency and abundance of regulatory T cells (Tregs) and Th17 cells shown to accompany disease progression. Production of pro-inflammatory, anti-tumor, and tumor-promoting effector molecules demonstrated for each cell type as previously reviewed elsewhere [ 23 , 37 , 55 ]. The figure was generated using BioRender software.…”