An Increased Abundance of Tumor-Infiltrating Regulatory T Cells Is Correlated with the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma

• Published in: PloS one Vol. 9; no. 3; p. e91551
• Main Authors: Tang, Yichen, Xu, Xuejun, Guo, Shixiang, Zhang, Chaobin, Tang, Yan, Tian, Yi, Ni, Bing, Lu, Binfeng, Wang, Huaizhi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.03.2014; Public Library of Science (PLoS)
• Subjects: Abundance; Adenocarcinoma; Adult; Aged; Antigens; Biology and Life Sciences; Cancer therapies; Carcinoma, Pancreatic Ductal - immunology; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Case-Control Studies; CD25 antigen; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Colorectal cancer; Comparative analysis; Correlation; Cytokines; Cytometry; Cytotoxicity; Disease Progression; Epithelial cells; Female; Flow cytometry; Forkhead Transcription Factors - metabolism; Foxp3 protein; Hospitals; Humans; Immunity; Immunology; Immunophenotyping; Immunoregulation; Immunosuppression; Immunotherapy; Leukocytes (mononuclear); Liver cancer; Lymphocyte Count; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical prognosis; Medical research; Medicine and Health Sciences; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Ovarian cancer; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Patients; Peripheral blood mononuclear cells; Prognosis; Research and Analysis Methods; Stroma; Studies; Surgery; T cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tissues; Tumor Microenvironment; Tumors; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091551

CD4+CD25+Foxp3+ regulatory T cells (Tregs) can inhibit cytotoxic responses. Though several studies have analyzed Treg frequency in the peripheral blood mononuclear cells (PBMCs) of pancreatic ductal adenocarcinoma (PDA) patients using flow cytometry (FCM), few studies have examined how intratumoral Tregs might contribute to immunosuppression in the tumor microenvironment. Thus, the potential role of intratumoral Tregs in PDA patients remains to be elucidated. In this study, we found that the percentages of Tregs, CD4+ T cells and CD8+ T cells were all increased significantly in tumor tissue compared to control pancreatic tissue, as assessed via FCM, whereas the percentages of these cell types in PBMCs did not differ between PDA patients and healthy volunteers. The percentages of CD8+ T cells in tumors were significantly lower than in PDA patient PBMCs. In addition, the relative numbers of CD4+CD25+Foxp3+ Tregs and CD8+ T cells were negatively correlated in the tissue of PDA patients, and the abundance of Tregs was significantly correlated with tumor differentiation. Additionally, Foxp3+ T cells were observed more frequently in juxtatumoral stroma (immediately adjacent to the tumor epithelial cells). Patients showing an increased prevalence of Foxp3+ T cells had a poorer prognosis, which was an independent factor for patient survival. These results suggest that Tregs may promote PDA progression by inhibiting the antitumor immunity of CD8+ T cells at local intratumoral sites. Moreover, a high proportion of Tregs in tumor tissues may reflect suppressed antitumor immunity.