Indole-3-carbinol inhibits immune evasion in esophageal carcinoma by regulating CES1

Immunotherapy is a new treatment method for solid tumors, but its effect on esophageal carcinoma (ESCA) is not as good as expected. Indole-3-carbinol (I3C) has been demonstrated to have anti-cancer effect. This study aimed to investigate the effect of I3C on immune evasion and the molecular mechanism. T cell percentage was analyzed using flow cytometry and T cell killing ability was evaluated using a lactate dehydrogenase kit and enzyme-linked immunosorbent assay. The molecular mechanism was explored based on bioinformatic analysis, quantitative real-time polymerase chain reaction, RNA binding protein immunoprecipitation, and dual-luciferase reporter assay. The results indicated that I3C inhibited ESCA cell viability, increased CD3 ⁺ CD4 ⁺ and CD3 ⁺ CD8 ⁺ T cells, cytotoxic rate, as well as IFN-γ and IL-2 levels, suggesting that immune evasion was suppressed by I3C. Moreover, I3C elevated the expression of CES1, which expression was decreased in ESCA. Besides, CES1 interacted with PD-L1 to increase its expression. Rescue experiments demonstrated the effect of the I3C/CES1/PD-L1 axis on immune escape. Taken together, I3C suppresses immune evasion in ESCA by increasing CES1 expression, which interacts with PD-L1. These findings suggest that I3C may be used to improve the effectiveness of immunotherapy.