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:

HEPATOCELLULAR CARCINOMA

CXCR2 inhibition in NASH-HCC

Nature Reviews Gastroenterology & Hepatology volume 19, page 415 (2022)Cite this article

Subjects

Treatment options for advanced hepatocellular carcinoma (HCC) include immune checkpoint inhibitors (ICIs) such as anti-PD1, but not all patients with nonalcoholic steatohepatitis (NASH)-driven HCC respond to immunotherapy. A new study in Gut elucidates the role of neutrophils in NASH-HCC and suggests a novel therapeutic avenue for immunotherapy improvement.

NASH-HCC mouse models responded suboptimally to CXCR2 inhibition or anti-PD1 treatment alone, but when the researchers proceeded with CXCR2 inhibition combined with anti-PD1 therapy, they observed reduced tumour burden and improved survival. Further analysis demonstrated that the combination therapy increased CD8+ antitumoural T cells, which clustered with neutrophils inside the mouse tumours, and secreted the tumour cytotoxic molecule granzyme B. It was also shown that activation of dendritic cells enabled the T cell-mediated antitumoural response. In addition, combination therapy surprisingly increased numbers of TANs in NASH-HCC mouse tumours, and transcriptomic analysis revealed a neutrophil-reprogramming molecular signature associated with stimulation of tumour adaptive immunity.

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

Download references

Author information

Authors and Affiliations

  1. Nature Reviews Gastroenterology & Hepatology http://www.nature.com/nrgastro/

    Eleni Kotsiliti

Authors
  1. Eleni Kotsiliti
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Eleni Kotsiliti.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kotsiliti, E. CXCR2 inhibition in NASH-HCC. Nat Rev Gastroenterol Hepatol 19, 415 (2022). https://doi.org/10.1038/s41575-022-00637-3

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41575-022-00637-3

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