Immunopathogenesis and therapy of cutaneous T cell lymphoma
Ellen J. Kim, … , Maria Wysocka, Alain H. Rook
Ellen J. Kim, … , Maria Wysocka, Alain H. Rook
Published April 1, 2005
Citation Information: J Clin Invest. 2005;115(4):798-812. https://doi.org/10.1172/JCI24826.
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Science in Medicine

Immunopathogenesis and therapy of cutaneous T cell lymphoma

Abstract

Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally derived, skin-invasive T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of CTCLs and are characterized by malignant CD4+/CLA+/CCR4+ T cells that also lack the usual T cell surface markers CD7 and/or CD26. As MF/SS advances, the clonal dominance of the malignant cells results in the expression of predominantly Th2 cytokines, progressive immune dysregulation in patients, and further tumor cell growth. This review summarizes recent insights into the pathogenesis and immunobiology of MF/SS and how these have shaped current therapeutic approaches, in particular the growing emphasis on enhancement of host antitumor immune responses as the key to successful therapy.

Authors

Ellen J. Kim, Stephen Hess, Stephen K. Richardson, Sara Newton, Louise C. Showe, Bernice M. Benoit, Ravi Ubriani, Carmela C. Vittorio, Jacqueline M. Junkins-Hopkins, Maria Wysocka, Alain H. Rook

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Multimodality strategy for enhancing the antitumor response using immuno...
Multimodality strategy for enhancing the antitumor response using immunotherapeutics. A multimodality approach encompasses the activation of multiple arms of the immune response through the use of agents to activate DCs, CTLs (CD8+), and NK cells (CD56+). GM-CSF may enhance the numbers of DCs while agents that enhance CD40 expression (IFN-γ) and activation (CD40 ligand; activating anti-CD40 antibody) and TLR ligands (CpG-ODNs; imidazoquinolines) lead to DC cytokine production and to enhanced DC processing of apoptotic malignant T cells. Cytokines produced by DCs as well as exogenously administered cytokines augment CD8+ T cell and possibly NK cell cytolytic activity against the tumor cells. RAR-specific retinoids stimulate DC and CD8+ T cell cytokine production. Proapoptotic agents, including bexarotene, RAR-specific retinoids, PUVA, photopheresis, topical chemotherapy, total skin electron beam irradiation (TSEB), and denileukin diftitox, can assist in the development of an antitumor immune response by reducing the overall tumor burden and by providing a source of apoptotic malignant cells and tumor antigens for uptake by DCs.