Tumor-induced thymic involution via inhibition of IL-7R alpha and its JAK-STAT signaling pathway: protection by black tea.

ABSTRACT

Down-regulation of cell-mediated immune functions occurring at late stages of cancer may be related to the thymic involution since thymus is the major site of T cell maturation, proliferation, and differentiation. We found that in Ehrlich's ascites carcinoma (EAC)-bearing mice there was profound depletion of CD4+ and CD8+ cells in peripheral blood with severely damaged thymus on 21st day of tumor inoculation. However, treatment with black tea at an antitumor dose of 2.5% significantly reduced such depletion and protected the thymus considerably from tumor onslaught. A search for the underlying mechanism revealed EAC-induced IL-7Ralpha down-regulation, inhibition of JAK3 and STAT5 phosphorylation, and decrease in Bcl-2/Bax ratio in thymocytes that finally led to thymocyte apoptosis in one hand and T cell maturation block on the other. Interestingly, black tea treatment prevented IL-7Ralpha down-regulation and protected the signaling cascade through JAK-STAT thereby inhibiting tumor-induced thymic apoptosis and ensuring proper functioning of this organ in tumor-bearing host.