The Immunopathogenesis and Immunotherapy of Cutaneous T Cell Lymphoma: Part I, Pathways and Targets for Immune Restoration and Tumor Eradication.

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Cutaneous T cell lymphomas (CTCLs) are malignancies of skin-trafficking T cells. Patients with advanced CTCL manifest immune dysfunction that predisposes to infection and suppresses the anti-tumor immune response. Therapies that stimulate immunity have produced superior progression free survival compared to conventional chemotherapy, reinforcing the importance of addressing the immune deficient state in the care of CTCL patients. Recent research has better defined the pathogenesis of these immune deficits, explaining the mechanisms of disease progression and revealing potential therapeutic targets. The features of the malignant cell in mycosis fungoides (MF) and Sézary syndrome (SS) are now significantly better understood, including TH2 phenotype, Treg cytokine production, immune checkpoint molecule expression, chemokine receptors, and interactions with the microenvironment. The updated model of CTCL immunopathogenesis provides understanding into clinical progression and therapeutic response.

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