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.

Cancer immunotherapy

Instructing macrophages to fight cancer

Nature Biomedical Engineering volume 2, pages 559–561 (2018)Cite this article

Subjects

Two drug-loaded nanoparticle formulations that preferentially accumulate within tumour-associated macrophages induce macrophage repolarization to a tumoricidal state that leads to potent antitumour activity in multiple murine models of cancer.

Tumour-associated macrophages (TAMs) are one of the dominant immune cell types present in the tumour microenvironment. Arising from local tissue macrophages and from infiltrating monocytes, TAMs typically undergo differentiation and activation after receiving cytokine signals such as colony stimulating factor 1 (CSF-1), interleukin-4 (IL-4), IL-10 and chemokine (CC motif) ligand 2 (CCL2), which are secreted in the tumour milieu1,2. Depending on the conjugation of signals that they are exposed to in the tumour microenvironment, and due to their phenotypic plasticity, TAMs can be polarized to effector subsets, such as tumoricidal and pro-inflammatory cells (M1 subtype), or tumour-promoting and anti-inflammatory cells (M2 subtype)3. M1 macrophages have a high capacity to promote antitumour immune responses, owing to their production of inflammatory cytokines (such as IL-6, IL-12, IL-23 and tumour necrosis factor-α (TNF-α)). They also release reactive oxygen species, and have heightened antigen-presentation capability through the increased expression of major histocompatibility complex (MHC) molecules. However, the tumour microenvironment often promotes the polarization of macrophages towards the tumour-permissive M2 phenotype, characterized by the expression of immunosuppressive cytokines (such as IL-10 or transforming growth factor-β (TGF-β)) and the stimulation of angiogenesis and invasiveness (for example, through the expression of vascular endothelial growth factor A (VEGF-A) and of matrix metalloproteinases, respectively). Furthermore, the phagocytic activity of macrophages against malignant cells can be inhibited by cancer cells via the expression of CD47, a factor that binds to signal regulatory protein α (SIRP-α) on macrophages to convey a ‘do not eat me’ signal4.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Two strategies for the repolarization of TAMs from a tumour-permissive M2 to a tumour-reactive M1 phenotype, to induce tumour-cell death.

References

  1. Mantovani, A., Sozzani, S., Locati, M., Allavena, P. & Sica, A. Trends Immunol. 23, 549–555 (2002).

    Article  PubMed  CAS  Google Scholar 

  2. Sica, A. & Bronte, V. J. Clin. Invest. 117, 1155–1166 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Mantovani, A., Schioppa, T., Porta, C., Allavena, P. & Sica, A. Cancer Metastasis Rev. 25, 315–322 (2006).

    Article  PubMed  Google Scholar 

  4. Willingham, S. B. et al. Proc. Natl Acad. Sci. USA 109, 6662–6667 (2012).

    Article  PubMed  Google Scholar 

  5. Mantovani, A., Marchesi, F., Malesci, A., Laghi, L. & Allavena, P. Nat. Rev. Clin. Oncol. 14, 399–416 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Ngambenjawong, C., Gustafson, H. H. & Pun, S. H. Adv. Drug Deliv. Rev. 114, 206–221 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Nywening, T. M. et al. Lancet Oncol. 17, 651–662 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Chao, M. P. et al. Cell 142, 699–713 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Cieslewicz, M. et al. Proc. Natl Acad. Sci. USA 110, 15919–15924 (2013).

    Article  PubMed  Google Scholar 

  10. Beatty, G. L. et al. Science 331, 1612–1616 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. De Henau, O. et al. Nature 539, 443–447 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Kaneda, M. M. et al. Nature 539, 437–442 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Rodell, C. B. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-018-0236-8 (2018).

  14. Kulkarni, A. et al. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-018-0254-6 (2018).

  15. Keliher, E. J. et al. Bioconjugate Chem. 22, 2383–2389 (2011).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bioengineering, University of Washington, Seattle, WA, USA

    Heather H. Gustafson & Suzie H. Pun

Authors
  1. Heather H. Gustafson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suzie H. Pun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suzie H. Pun.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gustafson, H.H., Pun, S.H. Instructing macrophages to fight cancer. Nat Biomed Eng 2, 559–561 (2018). https://doi.org/10.1038/s41551-018-0276-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-018-0276-0

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