Disruption of the thymic microenvironment is associated with thymic involution of transitional cell cancer.

INTRODUCTION: During bladder tumorigenesis, thymopoiesis is usually downregulated. Considering that the thymus is the site of most T-cell development, this phenomenon may be related to thymic involution. However, the mechanisms involved in this phenomenon remain to be elucidated.

MATERIALS AND METHODS: An MB 49 murine bladder tumor model was used to identify mechanisms that might underlie this process.

RESULTS: The thymuses of tumor-bearing mice showed less cellularity than those of healthy mice. Involution was found to be associated with less proliferation and more apoptosis of thymic epithelial cells (TEC). Foxn1, KGF, and IL-7, three factors known to be involved in thymic development, were also downregulated in the thymuses of tumor bearers. When these mice were intravenously injected with KGF, the thymic microenvironment, thymopoiesis, and T-cell differentiation all returned to near normal status.

CONCLUSIONS: The decreases in thymopoiesis and impaired T-cell differentiation may be attributable to changes in the thymic microenvironment. Improving the function of TEC, rather than T-cell progenitors, should be the focus of therapy.