Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer

// Ari J. Rosenberg 4, 9 , Derek A. Wainwright1, 2 , Alfred Rademaker 1, 3 , Carlos Galvez 4 , Matthew Genet 4 , Lijie Zhai 2 , Kristen L. Lauing 2 , Mary F. Mulcahy 1, 4, 9, 10 , John P. Hayes 1, 5 , David D. Odell 1, 6 , Craig Horbinski 1, 7 , Srinadh Komanduri 8 , Marie-Pier Tetreault 8 , Kwang-Youn A. Kim 3 and Victoria M. Villaflor 1, 4, 9, 10 1 Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, 60611 IL, USA 2 Department of Neurological Surgery, Feinberg School of Medicine of Northwestern University, Chicago, 60611 IL, USA 3 Department of Preventive Medicine, Feinberg School of Medicine of Northwestern University, Chicago, 60611 IL, USA 4 Department of Medicine, Feinberg School of Medicine of Northwestern University, Chicago, 60611 IL, USA 5 Department of Radiation Oncology, Northwestern University, Chicago, 60611 IL, USA 6 Department of Thoracic Surgery, Northwestern University, Chicago, 60611 IL, USA 7 Department of Pathology, Northwestern University, Chicago, 60611 IL, USA 8 Department of Gastroenterology, Northwestern University, Chicago, 60611 IL, USA 9 Division of Hematology and Oncology, Northwestern University, Chicago, 60611 IL, USA 10 Northwestern Medicine Developmental Therapeutics Institute, Chicago, 60611 IL, USA Correspondence to: Victoria M. Villaflor, email: Victoria.villaflor@nm.org Keywords: esophageal cancer; indoleamine 2,3 dioxygenase; immunotherapy; checkpoint inhibitor; the cancer genome atlas Received: December 23, 2017 Accepted: April 04, 2018 Published: May 04, 2018 ABSTRACT Background: Indoleamine 2,3-dioxygenase1 (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. Results: 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). 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 CD3e ( P < 0.0001). Conclusions: EC with high IDO1 and PD-L1expression 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 Methods: mRNA 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 CD3e, followed by light microscopic analysis.