title: CD4+CD25+ Treg derived from hepatocellular carcinoma mice inhibits tumor immunity.
abstract: CD4+CD25+ regulatory T cells (Tregs) play an essential role in the establishment and persistence of tumor immune suppression. Tregs can prevent anti-tumor-specific T cells from clearing the tumor, making Tregs a significant barrier for effective immunotherapy. An increase in the number of Tregs has been detected in the peripheral blood and tumor infiltrating lymphocytes of patients with hepatocellular carcinoma. Dendritic cells (DCs) are antigen-presenting cells that play a pivotal role in the initiation of immune responses. The evidence for their ability to act as natural adjuvant in the stimulation of specific anti-tumor cytotoxic T lymphocytes and in the induction of protective and therapeutic anti-tumor immunity is now overwhelming. The aim of our study was to investigate the variation of Tregs in hepatocellular carcinoma mice and how Tregs derived from the tumor mice affect DCs' function. We found that Tregs derived from the tumor mice down-regulated the expression of costimulatory molecules CD80/CD86 on DCs and inhibited the production of TNF-α and IL-12 from DCs. The suppressive function of Tregs was mediated by cell-to-cell contact, CTLA-4 expression and IL-10 secretion. In conclusion, these mechanisms acting in hepatocellular carcinoma may be necessary to better understand the immunosuppression of Tregs and helpful to the tumor immunotherapy.
authors.affiliation: Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D007109:Immunity / Q000276:immunology*; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4