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:

TUMOUR IMMUNOLOGY

Educating macrophages in melanoma

Nature Reviews Cancer volume 21, page 4 (2021)Cite this article

Subjects

While immune checkpoint inhibition (ICI) provides clinical benefit to a large proportion of patients with melanoma, a subset of patients is resistant to therapy. Mechanisms of ICI resistance can include dysfunction of infiltrated CD8+ T cells. In this study, Cerezo-Wallis et al. show that the melanoma-secreted growth factor midkine (MDK) drives an inflamed, immunosuppressive tumour microenvironment (TME), by promoting tumour-associated macrophage (TAM) phenotypes that induce CD8+ T cell dysfunction.

To test whether MDK promoted infiltration of immunosuppressive cells in the TME, the authors generated tumours in mice derived from MDK-negative human and mouse melanoma cell lines in which MDK was overexpressed through lentiviral transduction. Flow cytometry analysis showed that the TME of MDK-OE tumours compared with control tumours contained a high number of CD11b+Ly6ChighLy6G− cells expressing arginase 1 (ARG1+), which typically marks immunosuppressive myeloid cells as well as a high number of CD11b+F4/80highARG1+ cells (marking immunosuppressive TAMs). Importantly, purified MDK induced ARG1 expression in bone-marrow derived macrophages (BMDMs) significantly less than the melanoma-derived secretome did. Overall, this set of experiments indicated that autocrine MDK signalling might induce the secretion of immune cell modulators in melanoma cells.

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

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 Cancer http://www.nature.com/nrc/

    Ulrike Harjes

Authors
  1. Ulrike Harjes
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Ulrike Harjes.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harjes, U. Educating macrophages in melanoma. Nat Rev Cancer 21, 4 (2021). https://doi.org/10.1038/s41568-020-00317-x

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41568-020-00317-x

This article is cited by

Search

Advanced 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