Abstract
The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8(+) tumour-infiltrating lymphocytes (CD8(+) TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8(+) TILs. Patients with high IDO expression and a low number of CD8(+) TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8(+) TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8(+) TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / pathology
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Carcinoma, Squamous Cell / enzymology*
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Carcinoma, Squamous Cell / immunology*
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Carcinoma, Squamous Cell / pathology
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Carcinoma, Squamous Cell / physiopathology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Culture Media, Conditioned / pharmacology
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Cytotoxicity, Immunologic / drug effects
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Disease Progression
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Esophageal Neoplasms / enzymology*
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Esophageal Neoplasms / immunology*
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Esophageal Neoplasms / pathology
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Esophageal Neoplasms / physiopathology
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
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Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
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Interferon-gamma / metabolism
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Lymphocytes, Tumor-Infiltrating / drug effects
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / metabolism*
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Lymphocytes, Tumor-Infiltrating / pathology
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Male
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Neoplasm Staging
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Tumor Escape
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Tumor Microenvironment / immunology
Substances
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Culture Media, Conditioned
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Interferon-gamma