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.

TUMOR IMMUNOLOGY

Tpt1 the balance toward immunosuppression upon cell death

Nature Immunology volume 22, pages 940–942 (2021)Cite this article

Subjects

By engaging Toll-like receptor 2, translationally controlled tumor protein (TCTP) released from necrotic tumor cells can switch on an immunosuppressive network of monocytic and polymorphonuclear myeloid-derived suppressor cells to block antitumor immunity.

Accumulating evidence suggests that the release or exposure of damage-associated molecular patterns (DAMPs) can dictate the immunological consequences of cell death1. Multiple DAMPs have been reported as adjuvants that boost antitumor immunity2. However, all coins have two sides. In this issue of Nature Immunology, Hangai et al.3 discover that the release of the cytoplasmic protein TCTP (encoded by the gene Tpt1) from necrotic cancer cells substantially contributes to immunosuppression and tumor progression. Once detected by monocytic myeloid-derived suppressor cells (M-MDSCs) via Toll-like receptor (TLR)2, TCTP can stimulate the secretion of the chemokines CXCL1 and CXCL2 and facilitate the intratumoral accumulation of polymorphonuclear (PMN)-MDSCs, thus attenuating the antitumor activities of CD8+ T cells and natural killer (NK) cells. Importantly, antagonizing TCTP with a monoclonal antibody (55F3) or an antimalarial agent (dihydroartemisinin) significantly delays tumor progression and enhances the efficacy of PD-1 blockade in mice. Considering that the protumoral effect of the TCTP–PMN-MDSC axis seems also to be operating in patients with cancer, it is worthwhile to investigate the therapeutic potential of TCTP blockade and the corresponding predictive biomarkers for these patients.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: TCTP has immunomodulatory activity when released from necrotic cancer cells.

References

  1. Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L. & Kroemer, G. Nat. Rev. Immunol. 17, 97–111 (2017).

    CAS  Article  Google Scholar 

  2. Ma, Y., Pitt, J. M., Li, Q. & Yang, H. Immunol. Rev. 280, 194–206 (2017).

    CAS  Article  Google Scholar 

  3. Hangai, S. et al. Nat Immunol. https://doi.org/10.1038/s41590-021-00967-5 (2021).

  4. Yee, P. P. et al. Nat. Commun. 11, 5424 (2020).

    Article  Google Scholar 

  5. Yatim, N., Cullen, S. & Albert, M. L. Nat. Rev. Immunol. 17, 262–275 (2017).

    CAS  Article  Google Scholar 

  6. Ahrens, S. et al. Immunity 36, 635–645 (2012).

    CAS  Article  Google Scholar 

  7. Hangai, S. et al. Proc. Natl Acad. Sci. USA 113, 3844–3849 (2016).

    CAS  Article  Google Scholar 

  8. Seifert, L. et al. Nature 532, 245–249 (2016).

    CAS  Article  Google Scholar 

  9. Bommer, U.-A. Results Probl. Cell Differ. 64, 69–126 (2017).

    CAS  Article  Google Scholar 

  10. Bommer, U.-A. et al. Cell Commun. Signal. 15, 9 (2017).

    Article  Google Scholar 

  11. Sterle, H. A. et al. Br. J. Cancer 120, 128–138 (2019).

    CAS  Article  Google Scholar 

  12. Yang, X. D. et al. Nat. Med. 17, 87–95 (2011).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Yuting Ma

  2. Suzhou Institute of Systems Medicine, Suzhou, China

    Yuting Ma

Authors
  1. Yuting Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuting Ma.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ma, Y. Tpt1 the balance toward immunosuppression upon cell death. Nat Immunol 22, 940–942 (2021). https://doi.org/10.1038/s41590-021-00986-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41590-021-00986-2

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