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.

  • News & Views
  • Published:

Tumor immunology

The road not taken en route to T cell exhaustion

The first detailed investigation of CD8+ tumor-infiltrating T cell differentiation in the hours after cells enter a tumor has yielded an unexpected twist. Naive T cells veer away from effector fate and enter the path towards exhaustion much earlier than expected.

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

Access options

Buy this article

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

Fig. 1: En route to CD8+ T cell exhaustion.

References

  1. McLane, L. M., Abdel-Hakim, M. S. & Wherry, E. J. Annu. Rev. Immunol. 37, 457–495 (2019).

    Article  CAS  PubMed  Google Scholar 

  2. Blank, C. U. et al. Nat. Rev. Immunol. 19, 665–674 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rudloff, M. W. et al. Nat. Immunol. https://doi.org/10.1038/s41590-023-01578-y (2023).

    Article  PubMed  Google Scholar 

  4. Bertolino, P., Bowen, D. G., McCaughan, G. W. & Fazekas de St Groth, B. J. Immunol. 166, 5430–5438 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Waugh, K. A. et al. J. Immunol. 197, 1477–1488 (2016).

    Article  CAS  PubMed  Google Scholar 

  6. Mognol, G. P. et al. Proc. Natl. Acad. Sci. USA 114, E2776–E2785 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li, Z. et al. J. Exp. Med. 219, e20210749 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sen, D. R. et al. Science 354, 1165–1169 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Philip, M. et al. Nature 545, 452–456 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Martinez, G. J. et al. Immunity 42, 265–278 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Khan, O. et al. Nature 571, 211–218 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Schietinger, A. et al. Immunity 45, 389–401 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Isogawa, M., Chung, J., Murata, Y., Kakimi, K. & Chisari, F. V. PLoS Pathog. 9, e1003490 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hernández, J., Aung, S., Marquardt, K. & Sherman, L. A. J. Exp. Med. 196, 323–333 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Scholer, A., Hugues, S., Boissonnas, A., Fetler, L. & Amigorena, S. Immunity 28, 258–270 (2008).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank A. Rao for comments. P.G.H. acknowledges support from National Institutes of Health (NIH) grants AI040127 and AI109842, and La Jolla Institute for Immunology institutional funds. B.D. is a Cancer Research Institute Irvington fellow supported by the Cancer Research Institute (CRI4681).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Patrick G. Hogan.

Ethics declarations

Competing interests

P.G.H. is a founder of CalciMedica, Inc, and serves on its scientific advisory board. B.D. has no competing interests to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dash, B., Hogan, P.G. The road not taken en route to T cell exhaustion. Nat Immunol 24, 1402–1404 (2023). https://doi.org/10.1038/s41590-023-01596-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41590-023-01596-w

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer