TY - JOUR
T1 - Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer
AU - Rosenberg, Ari J.
AU - Wainwright, Derek A.
AU - Rademaker, Alfred
AU - Galvez, Carlos
AU - Genet, Matthew
AU - Zhai, Lijie
AU - Lauing, Kristen L.
AU - Mulcahy, Mary F.
AU - Hayes, John P.
AU - Odell, David D.
AU - Horbinski, Craig
AU - Komanduri, Srinadh
AU - Tetreault, Marie Pier
AU - Kim, Kwang Youn A.
AU - Villaflor, Victoria M.
N1 - Funding Information:
Funding for this project was obtained from the Daniel M. Hoyne Foundation and the Dixon Translational Research Grant, Northwestern University.
Publisher Copyright:
© Rosenberg et al.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Background: Indoleamine 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. 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 CD3ε (P < 0.0001). Conclusions: EC 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 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.
AB - Background: Indoleamine 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. 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 CD3ε (P < 0.0001). Conclusions: EC 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 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.
KW - Checkpoint inhibitor
KW - Esophageal cancer
KW - Immunotherapy
KW - Indoleamine 2,3 dioxygenase
KW - The cancer genome atlas
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U2 - 10.18632/oncotarget.25235
DO - 10.18632/oncotarget.25235
M3 - Article
C2 - 29805749
AN - SCOPUS:85046819292
SN - 1949-2553
VL - 9
SP - 23482
EP - 23493
JO - Oncotarget
JF - Oncotarget
IS - 34
ER -
