Regulation of TIM-3 expression in a human T cell line by tumor-conditioned media and cyclic AMP-dependent signaling

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Su Jin Yun, Bokyoung Lee, Kuniharu Komori, Mi Jin Lee, Byoung Gill Lee, Kyongmin Kim, Sun Park

Abstract

T cell immunoglobulin and mucin domain-3 (TIM-3) expression increases in exhausted T cells, which inhibits T cell function. TIM-3 expression is supposedly up-regulated in tumor-bearing individuals via chronic antigenic stimulation of T cells. Considering the immunosuppressive nature of the tumor microenvironment, we investigated whether tumor-secreted molecules might enhance TIM-3 expression in Jurkat T cells. We observed that TIM-3 expression was increased by the activation of prostaglandin (PG) E₂ and cyclic AMP (cAMP) signaling pathways. Adenylate cyclase activation led to protein kinase A (PKA)-dependent upregulation of the TIM-3 minimal promoter region and of upstream conserved non-coding sequences. TIM-3 expression in Jurkat T cells was increased by the exposure to breast tumor cell-conditioned media partially through the interaction between PGE₂ and its receptor, EP4. Our results propose that tumor-secreted molecules such as PGE₂, which activates PKA and EPAC, may regulate TIM-3 expression in T cells.

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