CD4 regulatory T cells in human cancer pathogenesis (original) (raw)
References
Hogquist KA, Baldwin TA, Jameson SC (2005) Central tolerance: learning self-control in the thymus. Nat Rev Immunol 5:772–782 PubMedCAS Google Scholar
Buckner JH, Ziegler SF (2004) Regulating the immune system: the induction of regulatory T cells in the periphery. Arthritis Res Ther 6:215–222 PubMedCAS Google Scholar
Redmond WL, Sherman LA (2005) Peripheral tolerance of CD8 T lymphocytes. Immunity 22:275–284 PubMedCAS Google Scholar
Kronenberg M, Rudensky A (2005) Regulation of immunity by self-reactive T cells. Nature 435:598–604 PubMedCAS Google Scholar
Mills KH, McGuirk P (2004) Antigen-specific regulatory T cells—their induction and role in infection. Semin Immunol 16:107–117 PubMedCAS Google Scholar
Wing K, Suri-Payer E, Rudin A (2005) CD4+CD25+-regulatory T cells from mouse to man. Scand J Immunol 62:1–15 PubMedCAS Google Scholar
Gregori S, Bacchetta R, Hauben E, Battaglia M, Roncarolo MG (2005) Regulatory T cells: prospective for clinical application in hematopoietic stem cell transplantation. Curr Opin Hematol 12:451–456 PubMed Google Scholar
Bacchetta R, Gregori S, Roncarolo MG (2005) CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun Rev 4:491–496 PubMed Google Scholar
Maggi E, Cosmi L, Liotta F, Romagnani P, Romagnani S, Annunziato F (2005) Thymic regulatory T cells. Autoimmun Rev 4:579–586 PubMedCAS Google Scholar
Lan RY, Ansari AA, Lian ZX, Gershwin ME (2005) Regulatory T cells: development, function and role in autoimmunity. Autoimmun Rev 4:351–363 PubMedCAS Google Scholar
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155:1151–1164 PubMedCAS Google Scholar
Moller G (1988) Do suppressor T cells exist? Scand J Immunol 27:247–250 PubMedCAS Google Scholar
Annunziato F, Cosmi L, Liotta F, Lazzeri E, Manetti R, Vanini V, Romagnani P, Maggi E, Romagnani S (2002) Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. J Exp Med 196:379–387 PubMedCAS Google Scholar
Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, Drebin JA, Strasberg SM, Eberlein TJ, Goedegebuure PS, Linehan DC (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169:2756–2761 PubMedCAS Google Scholar
Schaefer C, Kim GG, Albers A, Hoermann K, Myers EN, Whiteside TL (2005) Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br J Cancer 92:913–920 PubMedCAS Google Scholar
Okita R, Saeki T, Takashima S, Yamaguchi Y, Toge T (2005) CD4+CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer. Oncol Rep 14:1269–1273 PubMedCAS Google Scholar
Li X, Ye DF, Xie X, Chen HZ, Lu WG (2005) Proportion of CD4+CD25+ regulatory T cell is increased in the patients with ovarian carcinoma. Cancer Invest 23:399–403 PubMedCAS Google Scholar
Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B (2003) Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 9:606–612 PubMed Google Scholar
Stephens LA, Mottet C, Mason D, Powrie F (2001) Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro. Eur J Immunol 31:1247–1254 PubMedCAS Google Scholar
Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G (2001) Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193:1303–1310 PubMedCAS Google Scholar
Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4(+)CD25(high) regulatory cells in human peripheral blood. J Immunol 167:1245–1253 PubMedCAS Google Scholar
Cesana GC, DeRaffele G, Cohen S, Moroziewicz D, Mitcham J, Stoutenburg J, Cheung K, Hesdorffer C, Kim-Schulze S, Kaufman HL (2006) Characterization of CD4+CD25+ regulatory T cells in patients treated with high-dose interleukin-2 for metastatic melanoma or renal cell carcinoma. J Clin Oncol 24:1169–1177 PubMedCAS Google Scholar
Kono K, Kawaida H, Takahashi A, Sugai H, Mimura K, Miyagawa N, Omata H, Fujii H (2005) CD4(+)CD25(high) regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother. Epub ahead of print (DOI 10.1007/s00262-005-0092-8)
Ormandy LA, Hillemann T, Wedemeyer H, Manns MP, Greten TF, Korangy F (2005) Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res 65:2457–2464 PubMedCAS Google Scholar
Thornton AM, Donovan EE, Piccirillo CA, Shevach EM (2004) Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J Immunol 172:6519–6523 PubMedCAS Google Scholar
Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY (2005) A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 6:1142–1151 PubMedCAS Google Scholar
Fontenot JD, Rudensky AY (2005) A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6:331–337 PubMedCAS Google Scholar
Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY (2005) Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 22:329–341 PubMedCAS Google Scholar
Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, Zhang A, Dahm P, Chao N, Gilboa E, Vieweg J (2005) Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 115:3623–3633 PubMedCAS Google Scholar
Ochs HD, Ziegler SF, Torgerson TR (2005) FOXP3 acts as a rheostat of the immune response. Immunol Rev 203:156–164 PubMedCAS Google Scholar
Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly TE, Saulsbury FT, Chance PF, Ochs HD (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27:20–21 PubMedCAS Google Scholar
Powell BR, Buist NR, Stenzel P (1982) An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. J Pediatr 100:731–737 PubMedCAS Google Scholar
Bennett CL, Ochs HD (2001) IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr Opin Pediatr 13:533–538 PubMedCAS Google Scholar
Bennett CL, Brunkow ME, Ramsdell F, O’Briant KC, Zhu Q, Fuleihan RL, Shigeoka AO, Ochs HD, Chance PF (2001) A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA–>AAUGAA) leads to the IPEX syndrome. Immunogenetics 53:435–439 PubMedCAS Google Scholar
Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME (2001) X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 27:18–20 PubMedCAS Google Scholar
Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, Wilkinson JE, Galas D, Ziegler SF, Ramsdell F (2001) Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 27:68–73 PubMedCAS Google Scholar
Kobayashi I, Shiari R, Yamada M, Kawamura N, Okano M, Yara A, Iguchi A, Ishikawa N, Ariga T, Sakiyama Y, Ochs HD, Kobayashi K (2001) Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX). J Med Genet 38:874–876 PubMedCAS Google Scholar
Owen CJ, Jennings CE, Imrie H, Lachaux A, Bridges NA, Cheetham TD, Pearce SH (2003) Mutational analysis of the FOXP3 gene and evidence for genetic heterogeneity in the immunodysregulation, polyendocrinopathy, enteropathy syndrome. J Clin Endocrinol Metab 88:6034–6039 PubMedCAS Google Scholar
Wildin RS, Freitas A (2005) IPEX and FOXP3: clinical and research perspectives. J Autoimmun 25(Suppl.):56–62 PubMedCAS Google Scholar
Allan SE, Passerini L, Bacchetta R, Crellin N, Dai M, Orban PC, Ziegler SF, Roncarolo MG, Levings MK (2005) The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J Clin Invest 115:3276–3284 PubMedCAS Google Scholar
Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, Buckner JH, Ziegler SF (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 112:1437–1443 PubMedCAS Google Scholar
Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T (1990) LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med 171:1393–1405 PubMedCAS Google Scholar
Triebel F (2003) LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination. Trends Immunol 24:619–622 PubMedCAS Google Scholar
Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA (2004) Role of LAG-3 in regulatory T cells. Immunity 21:503–513 PubMedCAS Google Scholar
Baixeras E, Huard B, Miossec C, Jitsukawa S, Martin M, Hercend T, Auffray C, Triebel F, Piatier-Tonneau D (1992) Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J Exp Med 176:327–337 PubMedCAS Google Scholar
Nocentini G, Riccardi C (2005) GITR: a multifaceted regulator of immunity belonging to the tumor necrosis factor receptor superfamily. Eur J Immunol 35:1016–1022 PubMedCAS Google Scholar
Valmori D, Qian F, Ayyoub M, Renner C, Merlo A, Gnjatic S, Stockert E, Driscoll D, Lele S, Old LJ, Odunsi K (2006) Expression of synovial sarcoma X (SSX) antigens in epithelial ovarian cancer and identification of SSX-4 epitopes recognized by CD4+ T cells. Clin Cancer Res 12:398–404 PubMedCAS Google Scholar
Stassen M, Fondel S, Bopp T, Richter C, Muller C, Kubach J, Becker C, Knop J, Enk AH, Schmitt S, Schmitt E, Jonuleit H (2004) Human CD25+ regulatory T cells: two subsets defined by the integrins alpha 4 beta 7 or alpha 4 beta 1 confer distinct suppressive properties upon CD4+ T helper cells. Eur J Immunol 34:1303–1311 PubMedCAS Google Scholar
Jonuleit H, Schmitt E, Kakirman H, Stassen M, Knop J, Enk AH (2002) Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells. J Exp Med 196:255–260 PubMedCAS Google Scholar
Barchet W, Price JD, Cella M, Colonna M, Macmillan SK, Cobb JP, Thompson PA, Murphy KM, Atkinson JP, Kemper C (2005) Complement-induced regulatory T cells suppress T cell responses but allow for dendritic cell maturation. Blood 107:1497–1504 PubMed Google Scholar
Freeman CM, Chiu BC, Stolberg VR, Hu J, Zeibecoglou K, Lukacs NW, Lira SA, Kunkel SL, Chensue SW (2005) CCR8 is expressed by antigen-elicited, IL-10-producing CD4+CD25+ T cells, which regulate Th2-mediated granuloma formation in mice. J Immunol 174:1962–1970 PubMedCAS Google Scholar
Veldman C, Hohne A, Dieckmann D, Schuler G, Hertl M (2004) Type I regulatory T cells specific for desmoglein 3 are more frequently detected in healthy individuals than in patients with pemphigus vulgaris. J Immunol 172:6468–6475 PubMedCAS Google Scholar
Allez M, Mayer L (2004) Regulatory T cells: peace keepers in the gut. Inflamm Bowel Dis 10:666–676 PubMed Google Scholar
Veldman C, Pahl A, Beissert S, Hansen W, Buer J, Dieckmann D, Schuler G, Hertl M (2006) Inhibition of the transcription factor Foxp3 converts desmoglein 3-specific type 1 regulatory T cells into Th2-like cells. J Immunol 176:3215–3222 PubMedCAS Google Scholar
Weiner HL (2001) Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev 182:207–214 PubMedCAS Google Scholar
Nakamura K, Kitani A, Fuss I, Pedersen A, Harada N, Nawata H, Strober W (2004) TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol 172:834–842 PubMedCAS Google Scholar
Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ (2004) Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 21:589–601 PubMedCAS Google Scholar
Houot R, Perrot I, Garcia E, Durand I, Lebecque S (2006) Human CD4+CD25high regulatory T cells modulate myeloid but not plasmacytoid dendritic cells activation. J Immunol 176:5293–5298 PubMedCAS Google Scholar
Ghiringhelli F, Menard C, Terme M, Flament C, Taieb J, Chaput N, Puig PE, Novault S, Escudier B, Vivier E, Lecesne A, Robert C, Blay JY, Bernard J, Caillat-Zucman S, Freitas A, Tursz T, Wagner-Ballon O, Capron C, Vainchencker W, Martin F, Zitvogel L (2005) CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med 202:1075–1085 PubMedCAS Google Scholar
Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK (2001) Type 1 T regulatory cells. Immunol Rev 182:68–79 PubMedCAS Google Scholar
Zheng SG, Gray JD, Ohtsuka K, Yamagiwa S, Horwitz DA (2002) Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors. J Immunol 169:4183–4189 PubMedCAS Google Scholar
Iellem A, Mariani M, Lang R, Recalde H, Panina-Bordignon P, Sinigaglia F, D‘Ambrosio D (2001) Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. J Exp Med 194:847–853 PubMedCAS Google Scholar
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949 PubMedCAS Google Scholar
Yang ZZ, Novak AJ, Stenson MJ, Witzig TE, Ansell SM (2006) Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T-cells in B-cell non-Hodgkin lymphoma. Blood. Epub ahead of print (DOI 10.1182/blood-2005-08-3376)
Lim HW, Hillsamer P, Kim CH (2004) Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses. J Clin Invest 114:1640–1649 PubMedCAS Google Scholar
Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, Santarlasci V, Manetti R, Vanini V, Romagnani P, Maggi E, Romagnani S, Annunziato F (2003) Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood 102:4107–4114 PubMedCAS Google Scholar
Bruder D, Probst-Kepper M, Westendorf AM, Geffers R, Beissert S, Loser K, von Boehmer H, Buer J, Hansen W (2004) Neuropilin-1: a surface marker of regulatory T cells. Eur J Immunol 34:623–630 PubMedCAS Google Scholar
Masteller EL, Tang Q, Bluestone JA (2006) Antigen-specific regulatory T cells-ex vivo expansion and therapeutic potential. Semin Immunol 18:103–110 PubMedCAS Google Scholar
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998 PubMedCAS Google Scholar
Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111 PubMedCAS Google Scholar
Willimsky G, Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–146 PubMedCAS Google Scholar
Ercolini AM, Ladle BH, Manning EA, Pfannenstiel LW, Armstrong TD, Machiels JP, Bieler JG, Emens LA, Reilly RT, Jaffee EM (2005) Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response. J Exp Med 201:1591–1602 PubMedCAS Google Scholar
Ohlen C, Kalos M, Hong DJ, Shur AC, Greenberg PD (2001) Expression of a tolerizing tumor antigen in peripheral tissue does not preclude recovery of high-affinity CD8+ T cells or CTL immunotherapy of tumors expressing the antigen. J Immunol 166:2863–2870 PubMedCAS Google Scholar
Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB, Moe R, Cheever MA (1994) Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 54:16–20 PubMedCAS Google Scholar
Disis ML, Knutson KL, Schiffman K, Rinn K, McNeel DG (2000) Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. Breast Cancer Res Treat 62:245–252 PubMedCAS Google Scholar
Rentzsch C, Kayser S, Stumm S, Watermann I, Walter S, Stevanovic S, Wallwiener D, Guckel B (2003) Evaluation of pre-existent immunity in patients with primary breast cancer: molecular and cellular assays to quantify antigen-specific T lymphocytes in peripheral blood mononuclear cells. Clin Cancer Res 9:4376–4386 PubMedCAS Google Scholar
Goodell V, Salazar LG, Urban N, Drescher CW, Gray H, Swensen RE, McIntosh MW, Disis ML (2006) Antibody immunity to the p53 oncogenic protein is a prognostic indicator in ovarian cancer. J Clin Oncol 24:762–768 PubMedCAS Google Scholar
Guckel B, Rentzsch C, Nastke MD, Marme A, Gruber I, Stevanovic S, Kayser S, Wallwiener D (2005) Pre-existing T-cell immunity against mucin-1 in breast cancer patients and healthy volunteers. J Cancer Res Clin Oncol 132:265–274 PubMed Google Scholar
Anichini A, Vegetti C, Mortarini R (2004) The paradox of T-cell-mediated antitumor immunity in spite of poor clinical outcome in human melanoma. Cancer Immunol Immunother 53:855–864 PubMed Google Scholar
Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348:203–213 PubMedCAS Google Scholar
Peoples GE, Goedegebuure PS, Smith R, Linehan DC, Yoshino I, Eberlein TJ (1995) Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci USA 92:432–436 PubMedCAS Google Scholar
Peoples GE, Anderson BW, Lee TV, Murray JL, Kudelka AP, Wharton JT, Ioannides CG (1999) Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyte-recognized antigen system in epithelial cancers. Clin Cancer Res 5:4214–4223 PubMedCAS Google Scholar
Delong P, Carroll RG, Henry AC, Tanaka T, Ahmad S, Leibowitz MS, Sterman DH, June CH, Albelda SM, Vonderheide RH (2005) Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma. Cancer Biol Ther 4:342–346 ArticlePubMedCAS Google Scholar
Wang HY, Lee DA, Peng G, Guo Z, Li Y, Kiniwa Y, Shevach EM, Wang RF (2004) Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20:107–118 PubMedCAS Google Scholar
Kwok WW, Ptacek NA, Liu AW, Buckner JH (2002) Use of class II tetramers for identification of CD4+ T cells. J Immunol Methods 268:71–81 PubMedCAS Google Scholar
Kawaida H, Kono K, Takahashi A, Sugai H, Mimura K, Miyagawa N, Omata H, Ooi A, Fujii H (2005) Distribution of CD4+CD25high regulatory T-cells in tumor-draining lymph nodes in patients with gastric cancer. J Surg Res 124:151–157 PubMedCAS Google Scholar
Matsuura K, Yamaguchi Y, Ueno H, Osaki A, Arihiro K, Toge T (2006) Maturation of dendritic cells and T-cell responses in sentinel lymph nodes from patients with breast carcinoma. Cancer 106:1227–1236 PubMedCAS Google Scholar
Fattorossi A, Battaglia A, Ferrandina G, Buzzonetti A, Legge F, Salutari V, Scambia G (2004) Lymphocyte composition of tumor draining lymph nodes from cervical and endometrial cancer patients. Gynecol Oncol 92:106–115 PubMedCAS Google Scholar
Viguier M, Lemaitre F, Verola O, Cho MS, Gorochov G, Dubertret L, Bachelez H, Kourilsky P, Ferradini L (2004) Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol 173:1444–1453 PubMedCAS Google Scholar
Stassen M, Schmitt E, Jonuleit H (2004) Human CD(4+)CD(25+) regulatory T cells and infectious tolerance. Transplantation 77:S23–S25 PubMed Google Scholar
Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H, Fu YX (2005) Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 201:779–791 PubMedCAS Google Scholar
Turk MJ, Guevara-Patino JA, Rizzuto GA, Engelhorn ME, Sakaguchi S, Houghton AN (2004) Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J Exp Med 200:771–782 PubMedCAS Google Scholar
Jones E, Dahm-Vicker M, Simon AK, Green A, Powrie F, Cerundolo V, Gallimore A (2002) Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun 2:1 PubMed Google Scholar
Albers AE, Ferris RL, Kim GG, Chikamatsu K, DeLeo AB, Whiteside TL (2005) Immune responses to p53 in patients with cancer: enrichment in tetramer+ p53 peptide-specific T cells and regulatory T cells at tumor sites. Cancer Immunol Immunother 54:1072–1081 PubMedCAS Google Scholar
Chen YQ, Shi HZ, Qin XJ, Mo WN, Liang XD, Huang ZX, Yang HB, Wu C (2005) CD4+CD25+ regulatory T lymphocytes in malignant pleural effusion. Am J Respir Crit Care Med 172:1434–1439 PubMed Google Scholar
Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH (2001) Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61:4766–4672 PubMedCAS Google Scholar
Leong PP, Mohammad R, Ibrahim N, Ithnin H, Abdullah M, Davis WC, Seow HF (2006) Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast. Immunol Lett 102:229–236 PubMedCAS Google Scholar
Unitt E, Marshall A, Gelson W, Rushbrook SM, Davies S, Vowler SL, Morris LS, Coleman N, Alexander GJ (2006) Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantation. J Hepatol. DOI 10.101b.j.jhep.2005.12.027
Unitt E, Rushbrook SM, Marshall A, Davies S, Gibbs P, Morris LS, Coleman N, Alexander GJ (2005) Compromised lymphocytes infiltrate hepatocellular carcinoma: the role of T-regulatory cells. Hepatology 41:722–730 PubMedCAS Google Scholar
Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN, Vickers MA (2004) Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 103:1755–1762 PubMedCAS Google Scholar
Wei S, Kryczek I, Zou L, Daniel B, Cheng P, Mottram P, Curiel T, Lange A, Zou W (2005) Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res 65:5020–5026 PubMedCAS Google Scholar
Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Gastl G, Gunsilius E, Marth C (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11:8326–8331 PubMedCAS Google Scholar
Marth C, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Doppler W, Daxenbichler G (2004) Interferon-gamma expression is an independent prognostic factor in ovarian cancer. Am J Obstet Gynecol 191:1598–1605 PubMedCAS Google Scholar
Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, Mosseri V, Laccourreye O, Bruneval P, Fridman WH, Brasnu DF, Tartour E (2006) Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12:465–472 PubMedCAS Google Scholar
Alvaro T, Lejeune M, Salvado MT, Bosch R, Garcia JF, Jaen J, Banham AH, Roncador G, Montalban C, Piris MA (2005) Outcome in Hodgkin’s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res 11:1467–1473 PubMed Google Scholar
Cha Y, Holland SM, August JT (1990) The cDNA sequence of mouse LAMP-2. Evidence for two classes of lysosomal membrane glycoproteins. J Biol Chem 265:5008–5013 PubMedCAS Google Scholar
Setoguchi R, Hori S, Takahashi T, Sakaguchi S (2005) Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med 201:723–735 PubMedCAS Google Scholar
Roncarolo MG, Levings MK, Traversari C (2001) Differentiation of T regulatory cells by immature dendritic cells. J Exp Med 193:F5–F9 PubMedCAS Google Scholar
Awwad M, North RJ (1988) Immunologically mediated regression of a murine lymphoma after treatment with anti-L3T4 antibody. A consequence of removing L3T4+ suppressor T cells from a host generating predominantly Lyt-2+ T cell-mediated immunity. J Exp Med 168:2193–2206 PubMedCAS Google Scholar
North RJ (1982) Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med 155:1063–1074 PubMedCAS Google Scholar
Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6:295–307 PubMedCAS Google Scholar
Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H (2005) Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 105:2862–2868 PubMedCAS Google Scholar
Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59:3128–3133 PubMedCAS Google Scholar
Strassburg A, Pfister ED, Arning A, Nashan B, Ehrich JH, Melter M (2002) Basiliximab reduces acute liver allograft rejection in pediatric patients. Transplant Proc 34:2374–2375 PubMedCAS Google Scholar
Neuhaus P, Clavien PA, Kittur D, Salizzoni M, Rimola A, Abeywickrama K, Ortmann E, Chodoff L, Hall M, Korn A, Nashan B (2002) Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo-controlled trial. Liver Transpl 8:132–142 PubMed Google Scholar
Nashan B, Moore R, Amlot P, Schmidt AG, Abeywickrama K, Soulillou JP (1997) Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Lancet 350:1193–1198 PubMedCAS Google Scholar
Attia P, Powell DJ Jr, Maker AV, Kreitman RJ, Pastan I, Rosenberg SA (2006) Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2. J Immunother 29:208–214 PubMedCAS Google Scholar
Knutson KL, Dang Y, Lu H, Lukas J, Almand B, Gad E, Azeke E, Disis ML (2006) IL-2 immunotoxin therapy modulates tumor-associated regulatory T cells and leads to lasting immune-mediated rejection of breast cancers in neu-transgenic mice. J Immunol 177:84–91 PubMedCAS Google Scholar
Dutcher J (2002) Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma. Oncology (Williston Park) 16:4–10 Google Scholar
Egen JG, Kuhns MS, Allison JP (2002) CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 3:611–618 PubMedCAS Google Scholar
Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA (2003) Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 100:8372–8377 PubMedCAS Google Scholar
Maker AV, Attia P, Rosenberg SA (2005) Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade. J Immunol 175:7746–7754 PubMedCAS Google Scholar
Ko K, Yamazaki S, Makamura K, Nishioka T, Hirota K, Yamaguchi T, Shimizu J, Nomura T, Chiba T, Sakaguchi S (2005) Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J Exp Med 202:885–891 PubMedCAS Google Scholar
Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274 PubMedCAS Google Scholar
Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB (2004) Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 22:929–979 PubMedCAS Google Scholar
Chattopadhyay S, Chakraborty NG, Mukherji B (2005) Regulatory T cells and tumor immunity. Cancer Immunol Immunother 54:1153–1161 PubMed Google Scholar
Llorente L, Richaud-Patin Y, Garcia-Padilla C, Claret E, Jakez-Ocampo J, Cardiel MH, Alcocer-Varela J, Grangeot-Keros L, Alarcon-Segovia D, Wijdenes J, Galanaud P, Emilie D (2000) Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 43:1790–1800 PubMedCAS Google Scholar
Nobs L, Buchegger F, Gurny R, Allemann E (2006) Biodegradable nanoparticles for direct or two-step tumor immunotargeting. Bioconjug Chem 17:139–145 PubMedCAS Google Scholar
Nobs L, Buchegger F, Gurny R, Allemann E (2004) Current methods for attaching targeting ligands to liposomes and nanoparticles. J Pharm Sci 93:1980–1992 PubMedCAS Google Scholar