Natural killer reprogramming in cutaneous T-cell lymphomas: Facts and hypotheses

To better understand the pathogenesis of Sézary cells, distinguish them from reactive skin-infiltrating T-cells and improve disease treatment, efforts have been made to identify molecular targets deregulated by the malignant process. From immunophenotypic analysis and subtractive differential expression experiments to pan-genomic studies, many approaches have been used to identify markers of the disease. During the last decade several natural killer(NK) cell markers have been found aberrantly expressed at the surface of Sézary cells. In particular, KIR3DL2/CD158 k, expressed by less than 2% of healthy individuals CD4+ T-cells, is an excellent marker to identify and follow the tumor burden in the blood of Sézary syndrome patients. It may also represent a valuable target for specific immunotherapy. Other products of the NK cluster on chromosome 19q13 have been detected on Sézary cells, raising the hypothesis of an NK reprogramming process associated with the malignant transformation that may induce survival functions.

To better understand the pathogenesis of Sézary cells, distinguish them from reactive skin-infltrating T-cells and improve disease treatment, efforts have been made to identify molecular targets deregulated by the malignant process. From immunophenotypic analysis and subtractive differential expression experiments to pan-genomic studies, many approaches have been used to identify markers of the disease. During the last decade several natural killer （NK） cell markers have been found aberrantly expressed at the surface of Sézary cells. In particular, KIR3DL2/CD158k, expressed by less than 2% of healthy individuals CD4＋ T-cells, is an excellent marker to identify and follow the tumor burden in the blood of Sézary syndrome patients. It may also represent a valuable target for specifc im-munotherapy. Other products of the NK cluster on chromosome 19q13 have been detected on Sézary cells, raising the hypothesis of an NK reprogramming process associated with the malignant transformation that may induce survival functions.