Involvement of indoleamine 2,3-dioxygenase in impairing tumor-infiltrating CD8 T-cell functions in esophageal squamous cell carcinoma.
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.
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Ge
G
Zhang
Wan-Li
WL
Liu
Lin
L
Zhang
Jun-Ye
JY
Wang
Miao-Huan
MH
Kuang
Peng
P
Liu
Yue-Hao
YH
Lin
Shu-Qin
SQ
Dai
Jun
J
Du
D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000276:immunology
D017077:Culture Media, Conditioned; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma