title: MHC-mismatched mice liver transplantation promotes tumor growth in liver graft.
abstract: Liver transplantation is a final therapeutic option for treatment of hepatic malignancies, but local recurrence remains high after surgery. However, the underlying mechanisms of local tumor recurrence are still unknown. We speculated that immunological status of transplanted liver may contribute to the progress of tumor development. CT-26 tumor cells are injected into graft after allogeneic or syngeneic liver transplantation. The growth pattern of tumor and the co-relationship of regulatory T cell and effector T cells in liver graft were observed and investigated at 3d, 6d, 9d and 15d post-transplantation. The Hepatic Replacement Area of tumor in allogeneic grafts was significantly larger than that in syngeneic grafts. The activation of tumor growth in allografts was due to the dysfunction of effector T cells mediated by regulatory T cells in liver graft. Using nude mice model, we further confirmed that regulatory T cells from allograft significantly weaken the function of effector T cells in vivo. Our data has showed that MHC-mismatched mice liver transplantation can promote tumor growth in liver graft. For the first time, we demonstrated that susceptibility to tumor development in liver graft is due to the down-regulation of effector T cells' function mediated by the regulatory T cells.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yan
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Yufu
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Western Australia 6009, Australia. Electronic address: minghao.zheng@uwa.edu.au.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China; Key Laboratory of Organ Transplantation Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, PR China. Electronic address: shusenzheng@zju.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006648:Histocompatibility; D007155:Immunologic Factors / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D007155:Immunologic Factors
keywords: Allogeneic; Graft; Immune-environment; Liver transplantation; Mouse