STAT3 in T Cells: At The Crossroads of Inflammation and Cancer

Protocol Summary Constitutive STAT3 activity is implicated in many malignancies including Cutaneous T Cell Lymphoma. It is also essential for Th17 differentiation, a subset of CD4 effector T cell, implicated in chronic inflammatory conditions and possibly CTCL. HDAC inhibitors have shown activity in CTCL but their exact mechanism of action is not known. It is known that HDAC inhibitors regulate STAT3 transcriptional activity and hence can potentially be active in CTCL through modulation of the STAT3 pathway. The hypothesis is that Th17 cytokines contribute to the initiation of cancer by creating a pro-inflammatory microenvironment that predisposes cells to neoplastic transformation. To probe this, the investigators will compare the differences in cytokine production and gene expression in the skin resident T cells from patients with benign dermatoses and CTCL as well as in the blood/circulating lymphocytes of healthy donors and Sezary syndrome (SS). The investigators will also investigate whether HDAC inhibitors have a direct impact on the number of Th17 cells, the cytokine production by these cells and phosphorylated STAT3 protein in CTCL with subsequent treatment cycles. The objectives of this study are 1. Observe the epigenetic, transcriptional and phenotypic changes that take place in T cell during malignant transformation 2. Understand the mechanism of action of HDAC inhibitors in CTCL. Methods: Skin biopsy specimens from cutaneous T cell lymphoma (CTCL) patients and benign skin conditions namely eczema, dermatitis and psoriasis will be obtained through a standard punch biopsy procedure from the skin lesion. Additionally, 15 ml of peripheral blood from CTCL patients who have Sezary syndrome (SS) and from patients with benign skin condition will be collected. CTCL patients, who are starting treatment with HDAC Inhibitors namely Vorinostat and Romidepsin, will have a total of 3 skin biopsies and/or blood draws. The first procedure would be before starting tr