Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 3 , Pages 215-221 , September 2007

Regulatory T Cells: Potential Target in Anticancer Immunotherapy

  • Chi-Mou Juang

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • Institute of Epidemiology, College of Public Health, National Yang-Ming University, Taipei, Taiwan
    • Department of Pathology, Obstetrics and Gynecology, Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
    • ,
  • Chien-Fu Hung

      Affiliations

    • Department of Pathology, Obstetrics and Gynecology, Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
    • ,
  • Jiun-Yih Yeh

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Huann-Cheng Horng

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Nae-Fong Twu

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Ming-Huei Cheng

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Kuo-Chang Wen

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Chiou-Chung Yuan

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Kuan-Chong Chao

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • ,
  • T-C Wu

      Affiliations

    • Department of Pathology, Obstetrics and Gynecology, Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
    • ,
  • Ming-Shien Yen

      Affiliations

    • Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Ming-Shien Yen, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan

,Accepted 12 April 2007.

References 

  1. Houghton AN . Cancer antigens: immune recognition of self and altered self . J Exp Med . 1994;180:1–4
  2. Boon T , Cerottini JC , Van den Eynde B , van der Bruggen P , Van Pel A . Tumor antigens recognized by T lymphocytes . Annu Rev Immunol . 1994;12:337–365
  3. Hara I , Takechi Y , Houghton AN . Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein . J Exp Med . 1995;182:1609–1614
  4. Rosenberg SA , White DE . Vitiligo in patients with melanoma: normal tissue antigens can be targets for cancer immunotherapy . J Immunother Emphasis Tumor Immunol . 1996;19:81–84
  5. Berendt MJ , North RJ . T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor . J Exp Med . 1980;151:69–80
  6. North RJ . Down-regulation of the antitumor immune response . Adv Cancer Res . 1985;45:1–43
  7. Mukherji B , Wilhelm SA , Guha A , Ergin MT . Regulation of cellular immune response against autologous human melanoma. I. Evidence for cell-mediated suppression of in vitro cytotoxic immune response . J Immunol . 1986;136:1888–1892
  8. Mukherji B , Nashed AL , Guha A , Ergin MT . Regulation of cellular immune response against autologous human melanoma. II. Mechanism of induction and specificity of suppression . J Immunol . 1986;136:1893–1898
  9. Mukherji B, Guha A, Chakraborty NG, Sivanandham M, Nashed AL, Sporn JR, et al. Clonal analysis of cytotoxic and regulatory T cell responses against human melanoma . J Exp Med . 1989;169:1961–1976
  10. Sakaguchi S , Sakaguchi N , Asano M , Itoh M , Toda M . 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 . 1995;155:1151–1164
  11. Sakaguchi N , Miyai K , Sakaguchi S . Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells . J Immunol . 1994;152:2586–2595
  12. Fehervari Z , Sakaguchi S . CD4+ regulatory cells as a potential immunotherapy . Philos Trans R Soc Lond B Biol Sci . 2005;360:1647–1661
  13. Chattopadhyay S , Chakraborty NG , Mukherji B . Regulatory T cells and tumor immunity . Cancer Immunol Immunother . 2005;54:1153–1161
  14. Lan RY , Ansari AA , Lian ZX , Gershwin ME . Regulatory T cells: development, function and role in autoimmunity . Autoimmun Rev . 2005;4:351–363
  15. Sakaguchi S . Naturally arising Foxp3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self . Nat Immunol . 2005;6:345–352
  16. Saito S , Sasaki Y , Sakai M . CD4+ CD25high regulatory T cells in human pregnancy . J Reprod Immunol . 2005;65:111–120
  17. Bluestone JA , Abbas AK . Natural versus adaptive regulatory T cells . Nat Rev Immunol . 2003;3:253–257
  18. Sakaguchi S , Fukuma K , Kuribayashi K , Masuda T . Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease . J Exp Med . 1985;161:72–87
  19. Powrie F , Leach MW , Mauze S , et al.   Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice . Int Immunol . 1993;5:1461–1471
  20. Baecher-Allan C , Brown JA , Freeman GJ , Hafler DA . CD4+ CD25high regulatory cells in human peripheral blood . J Immunol . 2001;167:1245–1253
  21. Almeida AR , Legrand N , Papiernik M , Freitas AA . Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers . J Immunol . 2002;169:4850–4860
  22. Setoguchi R , Hori S , Takahashi T , Sakaguchi S . 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 . 2005;201:723–735
  23. Read S , Malmstrom V , Powrie F . Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation . J Exp Med . 2000;192:295–302
  24. Takahashi T , Tagami T , Yamazaki S , et al.   Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4 . J Exp Med . 2000;192:303–310
  25. Lehmann J , Huehn J , de la Rosa M , et al.   Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25-regulatory T cells . Proc Natl Acad Sci U S A . 2002;99:13031–13036
  26. McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, Collins M, et al. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor . Immunity . 2002;16:311–323
  27. Baecher-Allan C , Viglietta V , Hafler DA . Human CD4+ CD25+ regulatory T cells . Semin Immunol . 2004;16:89–98
  28. Cao D , Malmstrom V , Baecher-Allan C , Hafler D , Klareskog L , Trollmo C . Isolation and functional characterization of regulatory CD25bright CD4+ T cells from the target organ of patients with rheumatoid arthritis . Eur J Immunol . 2003;33:215–223
  29. Taams LS , Smith J , Rustin MH , Salmon M , Poulter LW , Akbar AN . Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone population . Eur J Immunol . 2001;31:1122–1131
  30. Lepault F , Gagnerault MC . Characterization of peripheral regulatory CD4+ T cells that prevent diabetes onset in nonobese diabetic mice . J Immunol . 2000;164:240–247
  31. Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, et al. Hassall's corpuscles instruct dendritic cells to induce CD4+ CD25+ regulatory T cells in human thymus . Nature . 2005;436:1181–1185
  32. Apostolou I , von Boehmer H . In vivo instruction of suppressor commitment in naive T cells . J Exp Med . 2004;199:1401–1408
  33. Shevach EM . CD4+ CD25+ suppressor T cells: more questions than answers . Nat Rev Immunol . 2002;2:389–400
  34. 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;194:629–644
  35. Baecher-Allan C , Viglietta V , Hafler DA . Inhibition of human CD4(+)CD25(+high) regulatory T cell function . J Immunol . 2002;169:6210–6217
  36. Levings MK , Sangregorio R , Roncarolo MG . Human CD25(+)CD4(+) T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function . J Exp Med . 2001;193:1295–1302
  37. von Boehmer H . Mechanisms of suppression by suppressor T cells . Nat Immunol . 2005;6:338–344
  38. Kiessling R, Wasserman K, Horiguchi S, Kono K, Sjoberg J, Pisa P, et al. Tumor-induced immune dysfunction . Cancer Immunol Immunother . 1999;48:353–362
  39. Strand S , Galle PR . Immune evasion by tumours: involvement of the CD95 (APO-1/Fas) system and its clinical implications . Mol Med Today . 1998;4:63–68
  40. Ganss R , Arnold B , Hammerling GJ . Mini-review: overcoming tumor-intrinsic resistance to immune effector function . Eur J Immunol . 2004;34:2635–2641
  41. Hontsu S , Yoneyama H , Ueha S , et al.   Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice . Int Immunopharmacol . 2004;4:1785–1793
  42. Sakaguchi S . Regulatory T cells: key controllers of immuno-logic self-tolerance . Cell . 2000;101:455–458
  43. Takahashi T , Sakaguchi S . The role of regulatory T cells in controlling immunologic self-tolerance . Int Rev Cytol . 2003;225:1–32
  44. Ko K , Yamazaki S , Nakamura K , et al.   Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+ CD25+ CD4+ regulatory T cells . J Exp Med . 2005;202:885–891
  45. Onizuka S , Tawara I , Shimizu J , Sakaguchi S , Fujita T , Nakayama E . Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody . Cancer Res . 1999;59:3128–3133
  46. Jones E, Dahm-Vicker M, Simon AK, 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;2:1
  47. Schaefer C , Kim GG , Albers A , Hoermann K , Myers EN , Whiteside TL . Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer . Br J Cancer . 2005;92:913–920
  48. 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;9:606–612
  49. Ichihara F , Kono K , Takahashi A , Kawaida H , Sugai H , Fujii H . Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers . Clin Cancer Res . 2003;9:4404–4408
  50. Liyanage UK , Moore TT , Joo HG , et al.   Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adeno-carcinoma . J Immunol . 2002;169:2756–2761
  51. Gray CP , Arosio P , Hersey P . Heavy chain ferritin activates regulatory T cells by induction of changes in dendritic cells . Blood . 2002;99:3326–3334
  52. 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;163:5211–5218
  53. Sutmuller RP , van Duivenvoorde LM , van Elsas A , et al.   Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in anti-tumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses . J Exp Med . 2001;194:823–832
  54. Curiel TJ , Coukos G , Zou L , et al.   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival . Nat Med . 2004;10:942–949
  55. Baecher-Allan C , Anderson DE . Immune regulation in tumor-bearing hosts . Curr Opin Immunol . 2006;18:214–219
  56. Needham DJ , Lee JX , Beilharz MW . Intra-tumoural regulatory T cells: a potential new target in cancer immunotherapy . Biochem Biophys Res Commun . 2006;343:684–691
  57. Dranoff G . CTLA-4 blockade: unveiling immune regulation . J Clin Oncol . 2005;23:662–664
  58. Awwad M , North RJ . Cyclophosphamide-induced immuno-logically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells . Cancer Res . 1989;49:1649–1654
  59. Wolf D , Hochegger K , Wolf AM , et al.   CD4+ CD25+ regulatory T cells inhibit experimental anti-glomerular basement membrane glomerulonephritis in mice . J Am Soc Nephrol . 2005;16:1360–1370
  60. Kuzel TM . DAB(389)IL-2 (denileukin diftitox, ONTAK): review of clinical trials to date . Clin Lymphoma . 2000;1(Suppl 1):S33–S36
  61. Peng G , Guo Z , Kiniwa Y , et al.   Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function . Science . 2005;309:1380–1384
  62. Zhou X , Zheng L , Liu L , Xiang L , Yuan Z . T helper 2 immunity to hepatitis B surface antigen primed by gene-gun-mediated DNA vaccination can be shifted towards T helper 1 immunity by codelivery of CpG motif-containing oligodeoxynucleo-tides . Scand J Immunol . 2003;58:350–357
  63. Zhou X , Xie Y , Tao X , Zhang Z , Li Z , Fauquet CM . Characterization of DNAbeta associated with begomoviruses in China and evidence for co-evolution with their cognate viral DNA-A . J Gen Virol . 2003;84:237–247

PII: S1028-4559(08)60023-6

doi: 10.1016/S1028-4559(08)60023-6

Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 3 , Pages 215-221 , September 2007

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