Abstract
BackgroundIndoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC.ResultsHigh IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001).ConclusionsEC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC.Materials and MethodsmRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic analysis.
Highlights
Esophageal cancer is a major cause of morbidity and mortality in the United States and worldwide
High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036)
esophageal cancer (EC) with high IDO1 and programmed death ligand 1 (PD-L1) expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells
Summary
Esophageal cancer is a major cause of morbidity and mortality in the United States and worldwide. Despite advances in the treatment of esophageal and GEJ cancer, overall 5-year survival remains dismal [2]. Trastuzumab, a monoclonal antibody that targets epidermal growth factor receptor 2 (Her2), is an option for the minority of patients with esophageal AC and GEJ tumors that overexpress Her2 [6]. Ramicurumab is a monoclonal antibody that targets vascular endothelial growth factor receptor (VEGFR) and offers a marginal benefit [7, 8]. Despite these small steps towards improved systemic therapy options in advanced esophageal and GEJ cancer, there is critical clinical need to improve therapeutic efficacy. We utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC
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