title: The impact of CD4+ CD25+ T cells in the tumor microenvironment of hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the most common liver cancer. Therapeutic results are usually unsatisfactory because liver tumors recur often. Immunologic factors may be related to the recurrence of HCC; however, this possibility is mentioned only rarely.
  
  
  METHODS
  Thirty HCC patients undergoing hepatectomies were divided into 3 groups according to the diameters of their HCCs: group A (n = 8), diameter ≤3 cm; group B (n = 8), diameter >3 cm and ≤5 cm; and group C (n = 14), diameter >5 cm. T-lymphocytes from peripheral blood, nontumor liver tissue, and the HCC were analyzed.
  
  
  RESULTS
  The percentage of CD25+ in the CD4+ T cells did not differ between the peripheral blood and the nontumor liver tissue among the 3 groups. CD25+ cells were increased in the tumor tissue in group C patients (range, 6-41%; median, 22.9%; P = .003), compared to group A patients. The percentage of CD25+ in the CD4+ T cells in tumor tissue was positively correlated with tumor sizes (r = 0.556). These CD4+ CD25+ lymphocytes produced transforming growth factor-β and interferon-γ but not interleukin-10, and were anergic to plate-coated monoclonal antibodies (anti-CD3/anti-CD28). The characteristics of these antibodies were comparable to those of regulatory T cells. When the infiltration lymphocytes including CD4+ CD25+ T cells were added to the mixed lymphocyte reaction activated by autologous tumor lysate-pulsed dendritic cells, the proliferation of lymphocytes was inhibited.
  
  
  CONCLUSIONS
  The increase of CD4+ CD25+ T cells in the tumor microenvironment correlates with tumor sizes. These CD4+ CD25+ regulatory T cells appeared to suppress the immune response activated by dendritic cells.
authors.affiliation: Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University Medical School, Taoyuan, Taiwan. weichen@cgmh.org.tw
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Lee
authors.forename: Ting-Jung
authors.initials: TJ
authors.lastname: Wu
authors.forename: Hong-Shiue
authors.initials: HS
authors.lastname: Chou
authors.forename: Ming-Chin
authors.initials: MC
authors.lastname: Yu
authors.forename: Pao-Yueh
authors.initials: PY
authors.lastname: Hsu
authors.forename: Hsiu-Ying
authors.initials: HY
authors.lastname: Hsu
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006498:Hepatectomy; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma