Esophageal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 14, 2008; 14(38): 5797-5809
Published online Oct 14, 2008. doi: 10.3748/wjg.14.5797
Depletion of CD4+CD25+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma
Yi-Ling Chen, Jung-Hua Fang, Ming-Derg Lai, Yan-Shen Shan
Yi-Ling Chen, Department of Childhood Education and Nursery, Chia-Nan University of Pharmacy and Science, Tainan 70428, Taiwan, China
Jung-Hua Fang, Yan-Shen Shan, Department of Surgery, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 70428, Taiwan, China
Ming-Derg Lai, Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan, China
Author contributions: Chen YL performed research and wrote the manuscript, Shan YS designed the research and revised the manuscript, Fang JH helped to perform the research, Lai MD helped to modify the design of research.
Supported by Grant NSC93-2320-B41-010 and NSC93-2314-B-006-112 from the National Science Council, Taiwan, China
Correspondence to: Yan-Shen Shan, MD, PhD, Assistant Professor, Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan, China. ysshan@mail.ncku.edu.tw
Telephone: +886-6-2353535 Fax: +886-6-2766676
Received: March 8, 2008
Revised: September 23, 2008
Accepted: September 30, 2008
Published online: October 14, 2008
Abstract

AIM: To elucidate the distribution of CD4+CD25+ regulatory T cells (Tregs) in different lymphoid tissues and its local enhancement on tumor growth before and after depletion of CD4+CD25+ Tregs.

METHODS: Female ICR mice were gavaged with benzo[a]pyrene (BaP) to induce forestomach carcinoma. CD4+CD25+ Tregs were intraperitoneally depleted with monoclonal antibody PC61. These mice were divided into BaP-only, BaP + IgG, BaP + PC61, and control groups. The forestomach of mice was dissected for histological analysis, and tunnel test was performed for apoptosis of tumor cells. CD4+CD25+ Tregs were sorted from different lymphoid tissues and expression of Foxp3, IL-10, and chemokine receptors was analyzed by flow cytometry, semi-quantitative and real-time polymerase chain reaction.

RESULTS: The mice gavaged with only BaP showed increased forestomach papilloma and carcinoma at wk 16 and 32. The proportion of CD4+CD25+ Tregs was significantly higher in peri-stomach regional lymph nodes than in other lymphoid tissues. These CD4+CD25+ Tregs in regional lymph nodes expressed higher levels of Foxp3 and IL-10, enriched in the CD62L-subset, and CCR1 and CCR5 chemokine receptors. In mice gavaged with BaP + PC61, the number of tumor nodules and tumor volume decreased significantly with massive infiltrating cells and apoptosis of tumor cells. In the draining regional lymph nodes, the number of CD4+CD25+ Tregs also decreased significantly.

CONCLUSION: Inducible and activated CD4+CD25+ Tregs in the draining regional lymph nodes suppress host local immunity during tumor growth. Depletion of CD4+CD25+ Tregs can promote host local immunity to suppress tumor growth.

Keywords: CD4+CD25+ regulatory T cells, Forestomach tumor, Foxp3