IDO1 Expression Is Associated With Immune Tolerance and Poor Prognosis in Patients With Surgically Resected Esophageal Cancer.

Abstract

OBJECTIVES\nTo evaluate the relationship between indoleamine 2, 3-dioxygenase (IDO1) expression and tumoral immune status and clinical outcome in esophageal cancer.\n\n\nSUMMARY BACKGROUND DATA\nIDO1 is a primary enzyme that generates immunosuppressive metabolites such as tryptophan and kynurenine. Like the PD-1/PD-L1 pathway, IDO1 plays a major role in tumor immunology and is a potential immune-based therapeutic target.\n\n\nMETHODS\nThe expressions of IDO1, CD8 (a marker of cytotoxic T cells), FOXP3 [a marker of regulatory T cells (Treg)], and PD-L1 in 305 curatively resected esophageal cancers were evaluated by immunostaining.\n\n\nRESULTS\nOverall survival was significantly better in the IDO1 negative cases (n = 234) than in the IDO1 positive cases (n = 71) [log-rank P = 0.0041; hazard ratio (HR): 1.75; 95% confidence interval (CI): 1.12-2.67; P = 0.015]. CD8 high expression was significantly positively correlated with overall survival (log-rank P = 0.025) and low IDO1 expression (P = 0.044). The inverse correlation between CD8 and IDO1 expressions was confirmed by double immunostaining for IDO1 and CD8. Stratification based on IDO1 and CD8 expressions was also significantly associated with overall survival (log-rank P = 0.0024). In addition, the IDO1-positive group was correlated with high counts of FOXP3-positive cells (P = 0.020), but not with PD-L1 expression status (P = 0.19).\n\n\nCONCLUSIONS\nIDO1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. Combining the IDO1 and CD8 statuses enabled further classification of the clinical outcomes of patients.