Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers.

Background: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3CD4CD8), which are believed to enable or promote tumorigenesis.

Immune Cell Plasticity Allows for Resetting of Phenotype From Effector to Regulator With Combined Inhibition of Notch/eIF5A Pathways.

Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells caused by an altered immune balance in the pancreatic microenvironment. In humans as well as in mouse models, T cells are well recognized as key orchestrators of T1D, which is characterized by T helper (Th) 1 and Th17 cell bias and/or low/defective T-regulatory cells (Treg), and culminates in cytotoxic T-cell (CTL)-mediated destruction of β-cells. Refitting of immune cells toward the non-inflammatory phenotype in the pancreas may represent a way to prevent/treat T1D.

eIF5A inhibition influences T cell dynamics in the pancreatic microenvironment of the humanized mouse model of Type 1 Diabetes.

We have developed a transgenic mouse model of Type 1 Diabetes (T1D) in which human GAD65 is expressed in pancreatic β-cells, and human MHC-II is expressed on antigen presenting cells. Induced GAD65 antigen presentation activates T-cells, which initiates the downstream events leading to diabetes. In our humanized mice, we have shown downregulation of eukaryotic translation initiation factor 5 A (elF5A), expressed only in actively dividing mammalian cells.

Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer.

Background: Thyroid cancer and thyroid autoimmunity are considered opposite extremes of immune-responses. However, several studies have suggested that thyroid cancer coexists with autoimmune thyroid diseases like Hashimoto Thyroiditis (HT) and Graves disease (GD). We have shown that the risk of developing thyroid cancer is higher in patients with a silent form of autoimmune thyroid disease -Euthyroid Hashimoto Thyroiditis-(EHT).