The Correlation Between the Subsets of Tumor Infiltrating Memory T Cells and the Expression of Indoleamine 2,3-Dioxygenase in Gastric Cancer

Abstract

Although many researchers have concentrated on the mechanism of T cell anergy resulting from over-expression of Indoleamine 2,3-dioxygenase (IDO), it remains unclear what alterations will developed in memory T cells (Tm) under over-expression of IDO. Immunohistochemical staining for IDO expression in gastric cancer tissues (n=50) was carried out. Tumor-infiltrating memory Tm cells were counted by flow cytometry. The association between IDO expression and the subsets of tumor infiltrating Tm are discussed. The higher IDO expressions were significantly associated with deeper invasion (P=0.016) and higher frequencies (P=0.038) of lymph node metastasis. The lower tumor-infiltrating CD4+Tm were significantly associated with the advanced clinical stage (P=0.026) and lymph node metastasis (P=0.016). The lower percentages of CD8+Tm were significantly related to undifferentiated histological type (P=0.042) and lymph node metastasis (P=0.037). However, the lower percentage of CD8+Tem was significantly correlated to differentiated histological type (P=0.017), lower frequencies of lymph node metastasis (P=0.014), and earlier clinical stage (P=0.008). The higher IDO expression patients had significantly lower percentages of CD4+Tm (P=0.012) and CD8+Tm (P=0.033). Nevertheless, it was confirmed that the higher level of IDO expression correlated with higher percentages of CD8+Tm cells in univariate and multivariate analysis (P=0.011). IDO over-expression and Tm in tumor microenvironments were correlated with the disease stage and histological type of gastric cancer. Higher IDO expression was related to the lower percentage of CD4+Tm and CD8+Tm, whereas the higher level of IDO expression related with a higher percentage of CD8+Tem.