Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

CANCER IMMUNOTHERAPY

How to kill Treg cells for immunotherapy

Nature Cancer volume 1, pages 1134–1135 (2020)Cite this article

Subjects

Achieving depletion of regulatory T cells while sparing tumor-specific effector T cells has long remained an elusive goal of immunotherapy. A new study describing the development of an antibody to the cytokine receptor CD25 optimized to ensure depletion of regulatory T cells without blocking binding of the cytokine IL-2 will reinvigorate interest in this therapeutic avenue.

Initial clinical trials targeting CD25 to selectively achieve depletion of Treg cells used a humanized monoclonal antibody to CD25, daclizumab, previously approved by the US Food and Drug Administration, that was originally developed to dampen the immune response involved in allograft rejection6,7. Although it seems surprising that a drug originally developed to block Teff cells could be repurposed to preferentially target Treg cells and spare Teff cells, the underlying mechanism by which daclizumab functions made this concept plausible. Whereas Teff cell function is augmented by IL-2 signaling, Treg cells absolutely require this signal for survival and maintenance of their suppressive phenotype8. Since daclizumab works by blocking IL-2 from binding to its receptor, it was postulated that Treg cells, which are more abundant in the TME and have higher expression of CD25, would be more severely affected than would Teff cells by administration of this drug. Indeed, clinical trials showed impressive but not complete depletion of Treg cells and augmented anti-cancer vaccine responses with timely administration of daclizumab but, alas, no effects on tumor size or progression, which dampened further development of this concept7.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Anti-CD25NIB depletes organisms of Treg cells to enhance tumor killing.

References

  1. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M. J. Immunol. 155, 1151–1164 (1995).

    CAS  PubMed  Google Scholar 

  2. Onizuka, S. et al. Cancer Res. 59, 3128–3133 (1999).

    CAS  PubMed  Google Scholar 

  3. Woo, E. Y. et al. J. Immunol. 168, 4272–4276 (2002).

    Article  CAS  Google Scholar 

  4. Shang, B., Liu, Y., Jiang, S. J. & Liu, Y. Sci. Rep. 5, 15179 (2015).

    Article  CAS  Google Scholar 

  5. Solomon, I. et al. Nat. Cancer https://doi.org/10.1038/s43018-020-00133-0 (2020).

  6. Jacobs, J. F. et al. Clin. Cancer Res. 16, 5067–5078 (2010).

    Article  CAS  Google Scholar 

  7. Rech, A. J. et al. Sci. Transl. Med. 4, 134ra162 (2012).

    Article  Google Scholar 

  8. Thornton, A. M. & Shevach, E. M. J. Exp. Med. 188, 287–296 (1998).

    Article  CAS  Google Scholar 

  9. Arce Vargas, F. et al. Immunity 46, 577–586 (2017).

    Article  CAS  Google Scholar 

  10. van Elsas, A., Hurwitz, A. A. & Allison, J. P. J. Exp. Med. 190, 355–366 (1999).

    Article  Google Scholar 

  11. Suntharalingam, G. et al. N. Engl. J. Med. 355, 1018–1028 (2006).

    Article  CAS  Google Scholar 

  12. Loskog, A. et al. Leukemia 20, 1819–1828 (2006).

    Article  CAS  Google Scholar 

  13. Rafiq, S. et al. Nat. Biotechnol. 36, 847–856 (2018).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology, Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA

    Gavin I. Ellis & James L. Riley

Authors
  1. Gavin I. Ellis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James L. Riley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James L. Riley.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ellis, G.I., Riley, J.L. How to kill Treg cells for immunotherapy. Nat Cancer 1, 1134–1135 (2020). https://doi.org/10.1038/s43018-020-00155-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s43018-020-00155-8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing