PURPOSE OF REVIEW: Mycosis fungoides and Sézary syndrome arise from malignant T cells that reside in skin, and subsequently are capable of circulating between skin, lymph nodes, and blood. The pathophysiologic mechanisms that cause and result in different behaviors of the skin-homing-malignant T cells in different stages of cutaneous T-cell lymphoma (CTCL) are still unknown. It is hypothesized that the skin microenvironment which is composed by various immune cell subsets as well as their spatial distribution and T-cell interaction through different chemokines and cytokines have an important role in the development and pathogenesis of CTCL and will be addressed in this chapter. RECENT FINDINGS: Recent studies have discovered that malignant T cells in Sézary syndrome are of the central memory T-cell subset, whereas those in mycosis fungoides are nonrecirculating skin-resident effector memory T cells, and have shown a protumorigenic role of mast cells and macrophages in CTCL. In addition, it has been observed that malignant T cells may exhibit features of one of these three distinct phenotypes (forkhead box P3 + regulatory T-cell phenotype, Th2 phenotype, and Th17 phenotype) and are functionally exhausted through an increased expression of certain coinhibitory molecules, such as programmed death-1. SUMMARY: All these new findings could assist in the development of novel targeted therapies for CTCL.
PURPOSE OF REVIEW: Mycosis fungoides and Sézary syndrome arise from malignant T cells that reside in skin, and subsequently are capable of circulating between skin, lymph nodes, and blood. The pathophysiologic mechanisms that cause and result in different behaviors of the skin-homing-malignant T cells in different stages of cutaneous T-cell lymphoma (CTCL) are still unknown. It is hypothesized that the skin microenvironment which is composed by various immune cell subsets as well as their spatial distribution and T-cell interaction through different chemokines and cytokines have an important role in the development and pathogenesis of CTCL and will be addressed in this chapter. RECENT FINDINGS: Recent studies have discovered that malignant T cells in Sézary syndrome are of the central memory T-cell subset, whereas those in mycosis fungoides are nonrecirculating skin-resident effector memory T cells, and have shown a protumorigenic role of mast cells and macrophages in CTCL. In addition, it has been observed that malignant T cells may exhibit features of one of these three distinct phenotypes (forkhead box P3 + regulatory T-cell phenotype, Th2 phenotype, and Th17 phenotype) and are functionally exhausted through an increased expression of certain coinhibitory molecules, such as programmed death-1. SUMMARY: All these new findings could assist in the development of novel targeted therapies for CTCL.
Authors: Paola Ghione; Alison J Moskowitz; Nadia E K De Paola; Steven M Horwitz; Marco Ruella Journal: Curr Hematol Malig Rep Date: 2018-12 Impact factor: 3.952
Authors: Alyxzandria M Gaydosik; Dawn S Queen; Megan H Trager; Oleg E Akilov; Larisa J Geskin; Patrizia Fuschiotti Journal: Blood Date: 2020-10-08 Impact factor: 22.113
Authors: Brittney A Dinkel; Kimberly N Kremer; Meagan R Rollins; Michael J Medlyn; Karen E Hedin Journal: J Biol Chem Date: 2018-07-17 Impact factor: 5.157
Authors: Kimberly N Kremer; Brittney A Dinkel; Rosalie M Sterner; Douglas G Osborne; Dragan Jevremovic; Karen E Hedin Journal: Blood Date: 2017-07-10 Impact factor: 22.113