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Expert Review of Dermatology Volume 1, 2006 - Issue 4
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Review

Manipulating T regulatory cells in cancer immunotherapy

Jens Rüter Department of Medicine (Hematology and Medical Oncology), Tulane University School of Medicine, 1430 Tulane Avenue SL-78, New Orleans, LA 70112, USA. [email protected]
,
Brian G Barnett Department of Medicine (Hematology and Medical Oncology), Tulane University School of Medicine, 1430 Tulane Avenue SL-78, New Orleans, LA 70112, USA. [email protected]
,
Ilona Kryczek Department of Surgery, University of Michigan, 1500 East Medical Center Drive, Room TC2101, Ann Arbor, MI 48109–0346, USA. [email protected]
,
Michael J Brumlik Department of Medicine (Hematology and Medical Oncology), Tulane University School of Medicine, 1430 Tulane Avenue SL-78, New Orleans, LA 70112, USA. [email protected]
,
Benjamin J Daniel Department of Medicine (Hematology and Medical Oncology), Tulane University School of Medicine, 1430 Tulane Avenue SL-78, New Orleans, LA 70112, USA. [email protected]
,
George Coukos Center for Research on Reproduction and Women's Health, University of Pennsylvania, 1355 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. [email protected]
,
Weiping Zou Department of Surgery, University of Michigan, 1500 East Medical Center Drive, Room TC2101, Ann Arbor, MI 48109-0346, USA. [email protected]
&
Tyler J Curiel Department of Medicine (Hematology and Medical Oncology), Tulane University School of Medicine, 1430 Tulane Avenue SL-78, New Orleans, LA 70112, USA. [email protected]
 show all
Pages 589-597 | Published online: 10 Jan 2014

References

  • Pardoll D. Does the immune system see tumors as foreign or self? Ann. Rev. Immunol.21, 807–839 (2003).
  • Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer5(4), 263–274 (2005).
  • Gershon RK, Kondo K. Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology18(5), 723–737 (1970).
  • Awwad M, North RJ. 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(6), 2193–2206 (1988).
  • Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol.155(3), 1151–1164 (1995).
  • Bach JF. Regulatory T cells under scrutiny. Nat. Rev. Immunol.3(3), 189–198 (2003).
  • Shevach EM. CD4+ CD25+ suppressor T cells: more questions than answers. Nat. Rev. Immunol.2(6), 389–400 (2002).
  • Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol.4(4), 330–336 (2003).
  • Yagi H, Nomura T, Nakamura K et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int. Immunol.16(11), 1643–1656 (2004).
  • Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol.3(3), 199–210 (2003).
  • von Herrath MG, Harrison LC. Antigen-induced regulatory T cells in autoimmunity. Nat. Rev. Immunol.3(3), 223–232 (2003).
  • Taylor PA, Noelle RJ, Blazar BR. CD4+CD25+ immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade. J. Exp. Med.193(11), 1311–1318 (2001).
  • Nishikawa H, Jager E, Ritter G, Old LJ, Gnjatic S. CD4+ CD25+ regulatory T cells control the induction of antigen-specific CD4+ helper T cell responses in cancer patients. Blood106(3), 1008–1011 (2005).
  • Chen ML, Pittet MJ, Gorelik L et al. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivo. Proc. Natl Acad. Sci. USA102(2), 419–424 (2005).
  • 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.193(11), 1295–1302 (2001).
  • Wang RF. Immune suppression by tumor-specific CD4+ regulatory T-cells in cancer. Semin. Cancer Biol.16(1), 73–79 (2006).
  • 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.163(10), 5211–5218 (1999).
  • Tanaka H, Tanaka J, Kjaergaard J, Shu S. Depletion of CD4+ CD25+ regulatory cells augments the generation of specific immune T cells in tumor-draining lymph nodes. J. Immunother.25(3), 207–217 (2002).
  • Steitz J, Bruck J, Lenz J, Knop J, Tuting T. Depletion of CD25+ CD4+ T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the interferon α-induced, CD8+ T-cell-dependent immune defense of B16 melanoma. Cancer Res.61(24), 8643–8646 (2001).
  • 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 antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J. Exp. Med.194(6), 823–832 (2001).
  • Woo EY, Chu CS, Goletz TJ et al. 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(12), 4766–4772 (2001).
  • 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.10(9), 942–949 (2004).
  • Woo EY, Yeh H, Chu CS et al. Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J. Immunol.168(9), 4272–4276 (2002).
  • Javia LR, Rosenberg SA. CD4+CD25+ suppressor lymphocytes in the circulation of patients immunized against melanoma antigens. J. Immunother.26(1), 85–93 (2003).
  • Somasundaram R, Jacob L, Swoboda R 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-β. Cancer Res.62(18), 5267–5272 (2002).
  • Wolf AM, Wolf D, Steurer M et al. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin. Cancer Res.9(2), 606–612 (2003).
  • Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A. CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer98(5), 1089–1099 (2003).
  • 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 adenocarcinoma. J. Immunol.169(5), 2756–2761 (2002).
  • Wolf D, Wolf AM, Rumpold H et al. 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(23), 8326–8331 (2005).
  • Barnett B, Kryczek I, Cheng P, Zou W, Curiel TJ. Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am. J. Reprod. Immunol.54(6), 369–377 (2005).
  • Berger CL, Tigelaar R, Cohen J et al. Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells. Blood105(4), 1640–1647 (2005).
  • Kohm AP, McMahon JS, Podojil JR et al. Cutting edge: anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells. J. Immunol.176(6), 3301–3305 (2006).
  • Church AC. Clinical advances in therapies targeting the interleukin-2 receptor. QJM96(2), 91–102 (2003).
  • Frankel AE, Powell BL, Lilly MB. Diphtheria toxin conjugate therapy of cancer. Cancer Chemother. Biol. Response Modif.20, 301–313 (2002).
  • Foss F, Demierre MF, DiVenuti G. A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood106(2), 454–457 (2005).
  • Olsen E, Duvic M, Frankel A et al. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J. Clin. Oncol.19(2), 376–388 (2001).
  • Barnett B, Kryczek I, Cheng Pet al. Depleting regulatory T cells is associated with improved immunity and tumor clearance in human cancer. Presented at: American Association for Cancer Research Annual Meeting, San Diego, CA, USA (2005).
  • Dannull J, Su Z, Rizzieri D et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest.115(12), 3623–3633 (2005).
  • Attia P, Maker AV, Haworth LR, Rogers-Freezer L, Rosenberg SA. Inability of a fusion protein of IL-2 and diphtheria toxin (denileukin diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma. J. Immunother.28(6), 582–592 (2005).
  • Ahmadzadeh M, Rosenberg SA. IL-2 administration increases CD4+CD25hiFoxp3+ regulatory T cells in cancer patients. Blood107(6), 2409–2414 (2005).
  • Zhang H, Chua KS, Guimond M et al. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat. Med.11(11), 1238–1243 (2005).
  • Antony PA, Restifo NP. CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2. J. Immunother.28(2), 120–128 (2005).
  • Berd D, Mastrangelo MJ. Effect of low dose cyclophosphamide on the immune system of cancer patients: depletion of CD4+, 2H4+ suppressor-inducer T-cells. Cancer Res.48(6), 1671–1675 (1988).
  • Ghiringhelli F, Larmonier N, Schmitt E et al. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur. J. Immunol.34(2), 336–344 (2004).
  • Bass KK, Mastrangelo MJ. Immunopotentiation with low-dose cyclophosphamide in the active specific immunotherapy of cancer. Cancer Immunol. Immunother.47(1), 1–12 (1998).
  • Lutsiak ME, Semnani RT, De Pascalis R et al. Inhibition of CD4+25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood105(7), 2862–2868 (2005).
  • Shaked Y, Emmenegger U, Francia G et al. Low-dose metronomic combined with intermittent bolus-dose cyclophosphamide is an effective long-term chemotherapy treatment strategy. Cancer Res.65(16), 7045–7051 (2005).
  • Scrivener S, Goddard RV, Kaminski ER, Prentice AG. Abnormal T-cell function in B-cell chronic lymphocytic leukaemia. Leuk. Lymphoma44(3), 383–389 (2003).
  • Beyer M, Kochanek M, Darabi K et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood106(6), 2018–2025 (2005).
  • Nocentini G, Giunchi L, Ronchetti S et al. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc. Natl Acad. Sci. USA94(12), 6216–6221 (1997).
  • Gurney AL, Marsters SA, Huang RM et al. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR. Curr. Biol.9(4), 215–218 (1999).
  • Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol.3(2), 135–142 (2002).
  • Kanamaru F, Youngnak P, Hashiguchi M et al. Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells. J. Immunol.172(12), 7306–7314 (2004).
  • Levings MK, Sangregorio R, Sartirana C et al. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor β, but not interleukin 10, and are distinct from type 1 T regulatory cells. J. Exp. Med.196(10), 1335–1346 (2002).
  • Ko K, Yamazaki S, Nakamura K et al. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25vCD4+ regulatory T cells. J. Exp. Med.202(7), 885–891 (2005).
  • Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol.5(10), 987–995 (2004).
  • Peng G, Guo Z, Kiniwa Y et al. Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science309(5739), 1380–1384 (2005).
  • Yang Y, Huang CT, Huang X, Pardoll DM. Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat. Immunol.5(5), 508–515 (2004).
  • 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.192(2), 303–310 (2000).
  • 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.192(2), 295–302 (2000).
  • Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat. Immunol.3(7), 611–618 (2002).
  • Walunas TL, Bluestone JA. CTLA-4 regulates tolerance induction and T cell differentiation in vivo. J. Immunol.160(8), 3855–3860 (1998).
  • Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Ann. Rev. Immunol.19, 565–594 (2001).
  • Dranoff G. CTLA-4 blockade: unveiling immune regulation. J. Clin. Oncol.23(4), 662–664 (2005).
  • Maker AV, Attia P, Rosenberg SA. Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with CTLA-4 blockade. J. Immunol.175(11), 7746–7754 (2005).
  • Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity12(2), 121–127 (2000).
  • Tanaka T, Bai Z, Srinoulprasert Y et al. Chemokines in tumor progression and metastasis. Cancer Sci.96(6), 317–322 (2005).
  • Haringman JJ, Tak PP. Chemokine blockade: a new era in the treatment of rheumatoid arthritis? Arthritis Res. Ther.6(3), 93–97 (2004).
  • Carter PH. Chemokine receptor antagonism as an approach to anti-inflammatory therapy: ‘just right’ or plain wrong? Curr. Opin. Chem. Biol.6(4), 510–525 (2002).
  • Colonna M, Trinchieri G, Liu YJ. Plasmacytoid dendritic cells in immunity. Nat. Immunol.5(12), 1219–1226 (2004).
  • Wei S, Kryczek I, Zou W. Regulatory T cell compartmentalization and trafficking. Blood DOI 10.1182/blood-2006-01-0177 (2006).
  • Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature392(6673), 245–252 (1998).
  • Curiel TJ, Wei S, Dong H et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat. Med.9(5), 562–567 (2003).
  • Wei S, Kryczek I, Zou L et al. Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res.65(12), 5020–5026 (2005).
  • Zou W, Machelon V, Coulomb-L’Hermin A et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat. Med.7(12), 1339–1346 (2001).
  • Curiel TJ, Cheng P, Mottram P et al. Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer. Cancer Res.64(16), 5535–5538 (2004).
  • Donzella GA, Schols D, Lin SW et al. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat. Med.4(1), 72–77 (1998).
  • Hatse S, Princen K, De Clercq E et al. AMD3465, a monomacrocyclic CXCR4 antagonist and potent HIV entry inhibitor. Biochem. Pharmacol.70(5), 752–761 (2005).
  • De Clercq E. Potential clinical applications of the CXCR4 antagonist bicyclam AMD3100. Mini. Rev. Med. Chem.5(9), 805–824 (2005).
  • Dzionek A, Fuchs A, Schmidt P et al. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J. Immunol.165(11), 6037–6046 (2000).
  • Strome SE, Dong H, Tamura H et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res.63(19), 6501–6505 (2003).
  • Dong H, Strome SE, Salomao DR et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med.8(8), 793–800 (2002).
  • Krupnick AS, Gelman AE, Barchet W et al. Murine vascular endothelium activates and induces the generation of allogeneic CD4+25+Foxp3+ regulatory T cells. J. Immunol.175(10), 6265–6270 (2005).
  • Conejo-Garcia JR, Buckanovich RJ, Benencia F et al. Vascular leukocytes contribute to tumor vascularization. Blood105(2), 679–681 (2005).
  • Conejo-Garcia JR, Benencia F, Courreges MC et al. Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat. Med.10(9), 950–958 (2004).
  • Dikopoulos N, Bertoletti A, Kroger A et al. Type I IFN negatively regulates CD8+ T cell responses through IL-10-producing CD4+ T regulatory 1 cells. J. Immunol.174(1), 99–109 (2005).
  • Zhou G, Drake CG, Levitsky HI. Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood107(2), 628–636 (2006).
  • Almand B, Clark JI, Nikitina E et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J. Immunol.166(1), 678–689 (2001).
  • Terabe M, Swann J, Ambrosino E et al. A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J. Exp. Med.202(12), 1627–1633 (2005).
  • Sica GL, Choi IH, Zhu G et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity18(6), 849–861 (2003).
  • Prasad DV, Richards S, Mai XM, Dong C. B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity18(6), 863–873 (2003).
  • Kryczek I, Zou L, Rodriguez P et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J. Exp. Med.203(4), 871–881 (2006).
  • Kudo-Saito C, Schlom J, Camphausen K, Coleman CN, Hodge JW. The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors. Clin. Cancer Res.11(12), 4533–4544 (2005).

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