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GPNMB: a potent inducer of immunosuppression in cancer

Oncogene volume 41, pages 4573–4590 (2022)Cite this article

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Abstract

The immune system is comprised of both innate and adaptive immune cells, which, in the context of cancer, collectively function to eliminate tumor cells. However, tumors can actively sculpt the immune landscape to favor the establishment of an immunosuppressive microenvironment, which promotes tumor growth and progression to metastatic disease. Glycoprotein-NMB (GPNMB) is a transmembrane glycoprotein that is overexpressed in a variety of cancers. It can promote primary tumor growth and metastasis, and GPNMB expression correlates with poor prognosis and shorter recurrence-free survival in patients. There is growing evidence supporting an immunosuppressive role for GPNMB in the context of malignancy. This review provides a description of the emerging roles of GPNMB as an inducer of immunosuppression, with a particular focus on its role in mediating cancer progression by restraining pro-inflammatory innate and adaptive immune responses.

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Fig. 1: GPNMB modulates innate immunity by negatively regulating macrophage and dendritic cell pro-inflammatory responses.
Fig. 2: GPNMB modulates adaptive immunity by dampening T cell responses. GPNMB inhibits T cell activation, proliferation, and infiltration.
Fig. 3: GPNMB inhibition in combination with immune modulators for overcoming resistance to immunotherapeutic agents.

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Acknowledgements

We thank members of the Siegel laboratory for thoughtful discussions and critical reading of the manuscript. Work referenced from the author’s laboratory was supported by a Project grant to PMS from the Canadian Institutes of Health Research (CIHR PJT-153327). PMS is a McGill University William Dawson Scholar. Figures created with BioRender.com.

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Authors and Affiliations

  1. Goodman Cancer Institute, McGill University, Montréal, QC, Canada

    Anna-Maria Lazaratos, Matthew G. Annis & Peter M. Siegel

  2. Department of Medicine, McGill University, Montréal, QC, Canada

    Matthew G. Annis & Peter M. Siegel

  3. Department of Biochemistry, McGill University, Montréal, QC, Canada

    Peter M. Siegel

  4. Department of Anatomy and Cell Biology, McGill University, Montréal, QC, Canada

    Peter M. Siegel

  5. Department of Oncology, McGill University, Montréal, QC, Canada

    Peter M. Siegel

Authors
  1. Anna-Maria Lazaratos
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  2. Matthew G. Annis
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  3. Peter M. Siegel
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Contributions

AML conducted the literature search, wrote the first draft and contributed to writing of final draft. MGA and PMS contributed to writing and editing of final drafts.

Corresponding author

Correspondence to Peter M. Siegel.

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Lazaratos, AM., Annis, M.G. & Siegel, P.M. GPNMB: a potent inducer of immunosuppression in cancer. Oncogene 41, 4573–4590 (2022). https://doi.org/10.1038/s41388-022-02443-2

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  • DOI: https://doi.org/10.1038/s41388-022-02443-2

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