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.

  • Research Highlight
  • Published:

Cardio-oncology

Hormone therapy ameliorates ICI-related myocarditis in mice

Nature Reviews Cardiology volume 20, page 4 (2023)Cite this article

Subjects

Immune checkpoint inhibitors (ICIs), although effective for cancer treatment, can cause myocarditis, with some clinical observations suggesting that female patients are more susceptible. New data from mouse models recapitulate this female predisposition to ICI-related myocarditis in mice and provide mechanistic and biological plausibility. The findings also suggest that hormone therapy could help treat myocarditis by promoting the expression of MANF, a protein related to the unfolded protein response. “Our findings show the importance of hormone regulation of transcription in ICI-associated myocarditis, which can explain the observed sex-related differences in patients, and provide evidence of how hormones regulate myocytokines, which have a protective role in heart disease,” say Liuqing Yang and Chunru Lin, who jointly led the study together with Javid Moslehi.

Manf and Hspa5 expression in cardiomyocytes was induced by liganded oestrogen receptor-β and inhibited by liganded androgen receptor. However, ICI treatment decreased 17β-oestradiol serum levels, to a greater extent in female mice, and thereby inhibited oestrogen-dependent transcription of Manf and Hspa5. Finally, the researchers demonstrated that hormone-directed therapies during ICI treatment (oestrogen or an oestrogen receptor-β agonist in female mice or androgen depletion therapy in male mice) ameliorated ICI-related myocarditis.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

References

Original article

  • Zhang, Y. et al. Hormonal therapies up-regulate MANF and overcome female susceptibility to immune checkpoint inhibitor myocarditis. Sci. Transl. Med. 14, eabo1981 (2022)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

Authors
  1. Irene Fernández-Ruiz
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Irene Fernández-Ruiz.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fernández-Ruiz, I. Hormone therapy ameliorates ICI-related myocarditis in mice. Nat Rev Cardiol 20, 4 (2023). https://doi.org/10.1038/s41569-022-00807-5

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41569-022-00807-5

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