The Impact of Indoleamine 2,3-dioxygenase (IDO) Expression on Stage III Gastric Cancer

• Published in: Anticancer research Vol. 38; no. 6; pp. 3387 - 3392
• Main Authors: Nishi, Masaaki, Yoshikawa, Kozo, Higashijima, Jun, Tokunaga, Takuya, Kashihara, Hideya, Takasu, Chie, Ishikawa, Daichi, Wada, Yuma, Shimada, Mitsuo
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.06.2018
• Subjects: Adult; Aged; Aged, 80 and over; Attenuation; Cancer; Cell activation; Female; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gastrectomy; Gastric cancer; Humans; Immunohistochemistry; Immunological tolerance; Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis; Kaplan-Meier Estimate; Lymphocytes; Lymphocytes T; Male; Medical prognosis; Middle Aged; Multivariate Analysis; Neoplasm Staging; Patients; Prognosis; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Survival; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta1 - metabolism; Tryptophan 2,3-dioxygenase; regulatory T cells; Gastric cancer; indoleamine 2,3-dioxygenase
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.12605

Indoleamine 2,3-dioxygenase (IDO) down-regulates T cell activation, attenuates regulatory T cell (Treg) activation and is related to immune tolerance. The aim of the study was to clarify the significance of IDO expression and analyze the relationships between the expression of IDO, TGF-β, and Foxp3 in gastric cancer (GC). A total of 60 patients who underwent curative gastrectomy for stage III gastric cancer were included in the study. The expression of IDO, TGF-β, and Foxp3 was examined by immunohistochemistry and the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. IDO expression was not positively correlated with any of the factors examined. IDO expression was positively correlated with TGF-β expression (p<0.05), and TGF-β expression was positively correlated with FoxP3 expression (p<0.05). Overall survival (OS) rates were significantly poorer in the IDO-positive group compared to the IDO-negative group (3-year OS, 78.5% vs. 90%, respectively; p<0.05). Multivariate analysis confirmed IDO expression as independent prognostic factors in OS. Disease-free survival (DFS) was significantly poorer in the IDO-positive group compared to the IDO-negative group (3-year DFS, 59.3% vs. 69.3%, respectively; p<0.05). IDO is associated with poor prognosis and immuno-tolerance through attenuation of Treg activation in Stage III GC.