STAT3 in T Cells: At The Crossroads of Inflammation and Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 9/19/2018 |
| Start Date: | May 1, 2012 |
| End Date: | November 21, 2016 |
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 treatment with either of these HDAC inhibitors. Two more skin
biopsies and/or blood draws will be performed after first and second cycle of treatment.
Levels of Th17 cytokines, IL-17, IL -22 and pSTAT3 protein will be determined by IHC staining
in the skin and cytokine levels in the blood will be assayed by sandwich ELISA method.The
investigators will also assay the mRNA levels of the transcription factors of the different T
effector cells by qPCR.
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 treatment with either of these HDAC inhibitors. Two more skin
biopsies and/or blood draws will be performed after first and second cycle of treatment.
Levels of Th17 cytokines, IL-17, IL -22 and pSTAT3 protein will be determined by IHC staining
in the skin and cytokine levels in the blood will be assayed by sandwich ELISA method.The
investigators will also assay the mRNA levels of the transcription factors of the different T
effector cells by qPCR.
Inclusion Criteria:
- Adult patients with CTCL that are starting new form of treatment and adult patients
with benign dermatoses.
Exclusion Criteria:
- patients with lymphomas other than CTCL or leukemia
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