SpringerLink
Log in

Tregs

  • Living reference work entry
  • First Online:
Cancer Therapeutic Targets

  • 141 Accesses

Abstract

Regulatory T cells (Tregs) are a subtype of T cells with immune suppressive function and play a key role in immune self-tolerance. Its immune inhibitory function has been implicated as the important mechanism of immune evasion and immune tolerance of human cancers. Tregs suppress antitumor immune responses through soluble factor-mediated as well as cell surface molecule-dependent inhibition of T cells and antigen-presenting cells. A significant increase in Treg numbers in the peripheral blood and in the tumor microenvironment has been associated with poor prognosis in various solid tumors. Better understanding of the roles of Tregs in tumor immunity has provided the rationale for the development of therapeutic modalities targeting immunosuppressive effects of Tregs. A number of therapeutic approaches have been proposed including the depletion of Treg by targeting Treg surface markers or with chemotherapeutic agents, the blockade of Treg suppressive function through inhibition of Treg receptors, and the inhibition of Treg induction and trafficking.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

  • Ascierto PA, et al. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol. 2010;37(5):508–16.

    Article  CAS  PubMed  Google Scholar 

  • Attia P, et al. 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. 2005;28(6):582–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bates GJ, et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24(34):5373–80.

    Article  PubMed  Google Scholar 

  • Cohen AD, et al. Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res. 2006;66(9):4904–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curiel TJ, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–9.

    Article  CAS  PubMed  Google Scholar 

  • Daayana S, et al. Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia. Br J Cancer. 2010;102(7):1129–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dannull J, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005;115(12):3623–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elkord E, et al. Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4). Cancer Immunol Immunother. 2009;58(10):1657–67.

    Article  CAS  PubMed  Google Scholar 

  • Giatromanolaki A, et al. The presence of tumor-infiltrating FOXP3+ lymphocytes correlates with intratumoral angiogenesis in endometrial cancer. Gynecol Oncol. 2008;110(2):216–21.

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, et al. Intratumoral FOXP3 expression in infiltrating breast carcinoma: its association with clinicopathologic parameters and angiogenesis. Acta Oncol. 2007;46(6):792–7.

    Article  CAS  PubMed  Google Scholar 

  • Hiraoka N, et al. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006;12(18):5423–34.

    Article  CAS  PubMed  Google Scholar 

  • Kaneko H, et al. Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo. Exp Hematol. 2005;33(3):336–43.

    Article  CAS  PubMed  Google Scholar 

  • Kreitman RJ, et al. Responses in refractory hairy cell leukemia to a recombinant immunotoxin. Blood. 1999;94(10):3340–8.

    CAS  PubMed  Google Scholar 

  • Kreitman RJ, et al. Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol. 2000;18(8):1622–36.

    CAS  PubMed  Google Scholar 

  • Litzinger MT, et al. IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. Blood. 2007;110(9):3192–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahnke K, et al. Depletion of CD4 + CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. Int J Cancer. 2007;120(12):2723–33.

    Article  CAS  PubMed  Google Scholar 

  • Mitsui J, et al. Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals. Clin Cancer Res. 2010;16(10):2781–91.

    Article  CAS  PubMed  Google Scholar 

  • Morse MA, et al. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood. 2008;112(3):610–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nair S, et al. Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res. 2007;67(1):371–80.

    Article  CAS  PubMed  Google Scholar 

  • Piconese S, Valzasina B, Colombo MP. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J Exp Med. 2008;205(4):825–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Powell Jr DJ, et al. Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo. J Immunol. 2007;179(7):4919–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramirez-Montagut T, et al. Glucocorticoid-induced TNF receptor family related gene activation overcomes tolerance/ignorance to melanoma differentiation antigens and enhances antitumor immunity. J Immunol. 2006;176(11):6434–42.

    Article  CAS  PubMed  Google Scholar 

  • Rasku MA, et al. Transient T cell depletion causes regression of melanoma metastases. J Transl Med. 2008;6:12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann N Y Acad Sci. 2009;1174:99–106.

    Article  CAS  PubMed  Google Scholar 

  • Sasada T, et al. CD4 + CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer. 2003;98(5):1089–99.

    Article  PubMed  Google Scholar 

  • Schaer DA, Murphy JT, Wolchok JD. Modulation of GITR for cancer immunotherapy. Curr Opin Immunol. 2012;24(2):217–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki H, et al. Intratumoral CD8(+) T/FOXP3 (+) cell ratio is a predictive marker for survival in patients with colorectal cancer. Cancer Immunol Immunother. 2010;59(5):653–61.

    Article  CAS  PubMed  Google Scholar 

  • Tzankov A, et al. Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma. Haematologica. 2008;93(2):193–200.

    Article  CAS  PubMed  Google Scholar 

  • Wolf D, 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. 2005;11(23):8326–31.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Johns Hopkins University, Baltimore, MD, 21205, USA

    Jong Chul Park

  2. Georgetown-Lombardi Comprehensive Cancer Center, 3970 Reservoir Road, NW Research Building, Room E501, Washington, DC, 20057, USA

    Michael B. Atkins

Authors
  1. Jong Chul Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael B. Atkins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jong Chul Park .

Editor information

Editors and Affiliations

  1. Georgetown University Div. Hematology & Oncology, Washington, District of Columbia, USA

    John L. Marshall

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this entry

Cite this entry

Park, J., Atkins, M. (2013). Tregs. In: Marshall, J. (eds) Cancer Therapeutic Targets. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6613-0_63-3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6613-0_63-3

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6613-0

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation