• 1
    Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: GLOBOCAN 2000. Int J Cancer 2001; 94: 153156.
  • 2
    O'Grady J, Lake JR, Howdle PD. Malignant tumours of the liver. In: O'GradyJG, LakeJR, HowdlePD, eds. Comprehensive Clinical Hepatology. London: Harcourt Publishers, 2000: 25.2125.18.
  • 3
    El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999; 340: 745750.
  • 4
    Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver Transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693700.
  • 5
    Dick EA, Taylor-Robinson SD, Thomas HC, Gedroyc WMW. Ablative therapy for liver tumours. Gut 2002; 50: 733739.
  • 6
    Levy I, Sherman M. Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto. Gut 2002; 50: 881885.
  • 7
    Foss FM. Immunologic mechanisms of antitumour activity. Semin Oncol 2002; 29: 511.
  • 8
    Chavan SS, Chiplunkar SV. Immunophenotypes and cytotoxic functions of lymphocytes in patients with hepatocellular carcinoma. Tumori 1997; 83: 762767.
  • 9
    Wada Y, Nakashima O, Kutami R, Yamamoto O, Kojiro M. Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration. HEPATOLOGY 1998; 27: 407414.
  • 10
    Kawata A, Une Y, Hosokawa M, Uchino J, Kobayashi H. Tumor-infiltrating lymphocytes and prognosis of hepatocellular carcinoma. Jpn J Clin Oncol 1992; 22: 256263.
  • 11
    Chouaib S, Asselin-Paturel C, Mami-Chouaib F, Caignard A, Yves Blay J. The host-tumour immune conflict: from immunosuppression to resistance and destruction. Immunology Today 1997; 18: 493499.
  • 12
    Piccirillo CA, Shevach EM. Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol 2001; 167: 11371140.
  • 13
    Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998; 188: 287296.
  • 14
    Annunziato F, Cosmi L, Liotta F, Lazzeri E, Manetti R, Vanini V, et al. Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. J Exp Med 2002; 196: 379387.
  • 15
    Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003; 4: 337342.
  • 16
    Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4: 330336.
  • 17
    Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, Buckner JH, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 2003; 112: 14371443.
  • 18
    Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4+CD25+ T cells with regulatory properties isolated from peripheral blood. J Exp Med 2001; 193: 12851294.
  • 19
    Baecher-Allen C, Brown JA, Freeman GJ, Haffler DA. CD4+CD25high regulatory cells in human peripheral blood. J Immunol 2001; 167: 12451253.
  • 20
    Oida T, Zhang X, Goto M, Hachimura S, Totsuka M, Kaminogawa S, et al. CD4+CD25- T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism. J Immunol 2003; 170: 25162522.
  • 21
    Green EA, Gorelik L, McGregor CM, Tran EH, Flavell RA. CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc Natl Acad Sci U S A 2003; 100: 1087810883.
  • 22
    Nakamura K, Kitani A, Fuss I, Pedersen A, Harada N, Nawata H, et al. TGF-beta1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol 2004; 172: 834842.
  • 23
    Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 2001; 194: 629644.
  • 24
    Shevach EM. CD4+CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2002; 2: 389400.
  • 25
    Gallimore A, Sakaguchi S. Regulation of tumour immunity by CD25+ T cells. Immunology 2002; 107: 59.
  • 26
    Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumour microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 2002; 169: 27562761.
  • 27
    Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, et al. Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol 2002; 168: 42724276.
  • 28
    Somasundaram R, Jacob L, Swoboda R, Caputo L, Song H, Basak S, et al. Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta. Cancer Res 2002; 62: 52675272.
  • 29
    Onizuka S, Tawara I, Shimizu S, Sakaguchi S, Fujita T, Nakayama E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 1999; 59: 31283133.
  • 30
    Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 1999; 163: 52115218.
  • 31
    Jones E, Dahm-Vicker M, Simon A, Green A, Powrie F, Cerundolo V, et al. Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun 2002; 2: 112.
  • 32
    Freeman A, Morris LS, Mills AD, Stoeber K, Laskey RA, Williams GH, et al. Minichromosome maintenance proteins as biological markers of dysplasia and malignancy. Clin Cancer Res 1999; 5: 21212132.
  • 33
    Rodins K, Cheale M, Coleman N, Fox SB. Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: relationship to tumour dormancy and potential clinical utility. Clin Cancer Res 2002; 8: 10751081.
  • 34
    Akhurst RJ. TGF-beta antagonists: why suppress a tumor suppressor? J Clin Invest 2002; 109: 15331536.
  • 35
    Baisch H, Gerdes J. Simultaneous staining of exponentially growing versus plateau phase cells with the proliferation-associated antibody Ki-67 and propidium iodide: analysis by flow cytometry. Cell Tissue Kinet 1987; 20: 387391.
  • 36
    Tomiyama H, Matsuda T, Takiguchi M. Differentiation of human CD8(+) T cells from a memory to memory/effector phenotype. J Immunol 2002; 168: 55385550.
  • 37
    Mortarini R, Piris A, Maurichi A, Molla A, Bersani I, Bono A, et al. Lack of terminally differentiated tumour-specific CD8+ T cells at tumour site in spite of antitumour immunity to self-antigens in human metastatic melanoma. Cancer Res 2003; 63: 25352545.
  • 38
    Fu S, Yopp AC, Mao X, Chen D, Zhang N, Mao M, et al. CD4+ CD25+ CD62+ T-regulatory cell subset has optimal suppressive and proliferative potential. Am J Transplant 2004; 4: 6578.
  • 39
    Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003; 9: 606612.
  • 40
    Yoong K, Afford S, Jones R, Aujla P, Qin S, Price K, et al. Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. HEPATOLOGY 1999; 30: 100111.
  • 41
    Chen S, Akbar SM, Tanimoto K, Ninomiya T, Iuchi H, Michitaka K, et al. Absence of CD83-positive mature and activated dendritic cells at cancer nodules from patients with hepatocellular carcinoma: relevance to hepatocarcinogenesis. Cancer Lett 2000; 148: 4957.
  • 42
    Yamauchi K, Akbar SM, Horiike N, Michitaka K, Onji M. Increased serum levels of macrophage inflammatory protein-3alpha in hepatocellular carcinoma: relationship with clinical factors and prognostic importance during therapy. Int J Mol Med 2003; 11: 601605.
  • 43
    Geissmann F, Revy P, Regnault A, Lepelletier Y, Dy M, Brousse N, et al. TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells. J Immunol 1999; 162: 45674575.
  • 44
    Giannelli G, Fransvea E, Marinosci F, Bergamini C, Colucci S, Schiraldi O, et al. Transforming growth factor-beta 1 triggers hepatocellular caarcinoma invasiveness via alpha3beta1 integrin. Am J Pathol 2002; 161: 183193.
  • 45
    Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003; 9: 606612.
  • 46
    Zheng SG, Gray JD, Ohtsuka K, Yamagiwa S, Horwitz DA. Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors. J Immunol 2002; 169: 41834189.
  • 47
    Camara NO, Sebille F, Lechler RI. Human CD4+CD25+ regulatory cells have marked and sustained effects on CD8+ T cell activation. Eur J Immunol 2003; 33: 34733483.