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At therapeutic concentrations (100200 M, achievable via intratumoral delivery), I3A activates the AhR/cAMP response element-binding protein (CREB) axis in CD8 + T cells: specifically, AhR recruits CREB to the IFN- promoter, inducing CREB phosphorylation at Ser133 to amplify type 1 cytotoxic T cell (Tc1) differentiation and tumor cytotoxicity (113, 171)