Sun park
Ajou University, South Korea
Title: Regulation of TIM-3 expression in T cells by tumor-conditioned mediaRegulation of TIM-3 expression in T cells by tumor-conditioned media
Biography
Biography: Sun park
Abstract
T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) is well known as one of the immune check point molecules. TIM-3 expression is increased on exhausted T cells and senescent T cells in numerous immune diseases including cancers. However, the regulatory mechanisms of TIM-3 expression in cancers have not been well studied. Using Jurkat T cells, we examined TIM-3 regulatory mechanisms in condition similar to tumor microenvironment. TIM-3 mRNA and protein levels were increased by co-culture of Jurkat T cells with tumor cell lines and by incubation of them in tumor cell conditioned media. Given that cyclic adenosine monophosphate (cAMP) can be transferred from tumor cells to T cells, we examined the effect of cAMP signaling on TIM-3 expression. It was promoted by intracellular elevation of cAMP concentration and activation of cAMP downstream pathways. Further, inhibition of cAMP downstream pathway attenuated TIM-3 expression in Jurkat T cells cultured in tumor-CM as well as in Jurkat T cells stimulated with a cAMP elevating agent. Conclusively, this study suggests that TIM-3 expression in Jurkat T cells may be induced by tumor CM through activation of cAMP pathway.