Macrophages hijack anti-PD-1 therapy

Killock, David

doi:10.1038/nrclinonc.2017.79

Research Highlight
Published: 31 May 2017

Immunotherapy

Macrophages hijack anti-PD-1 therapy

David Killock

Nature Reviews Clinical Oncology volume 14, page 394 (2017)Cite this article

2017 Accesses
4 Citations
9 Altmetric
Metrics details

Subjects

Access through your institution

Buy or subscribe

Anti-PD-1 antibodies (αPD-1) can provide long-term clinical benefit, but only for a minority of patients with cancer; our understanding of the mechanisms of response or resistance to these agents is limited. Mikael Pittet and co-workers sought to address this knowledge gap by studying the pharmacokinetics and pharmacodynamics of αPD-1 within the complex tumour microenvironment.

Intravital microscopy was used to investigate, in real-time and at subcellular resolution, the interactions between αPD-1 and CD8⁺ T cells (which express PD-1), tumour-associated macrophages (TAMs), and tumour cells in a mouse model of cancer. Commenting on the major findings, Pittet explains: “binding of αPD-1 to T cells within tumours occurs soon after infusion, as expected, but αPD-1 are transferred from T cells to TAMs within only a few minutes.” Notably, evidence indicated that TAMs physically remove the antibodies from the surface of T cells, although phagocytosis was ruled out as the main mechanism of antibody sequestration. Instead, “αPD-1 uptake by TAMs depends both on the Fc domain of the antibody, particularly its glycosylation, and on Fcγ receptors (FcγRs) expressed by TAMs,” Pittet adds. These findings were recapitulated using primary human immune cells and an approved αPD-1, nivolumab, in vitro.

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

Access options

Access through your institution

Buy this article

Purchase on SpringerLink
Instant access to full article PDF

Buy now

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

References

Arlauckas, S. P. et al. In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci. Transl Med. 9, eaal3604 (2017)
Article Google Scholar

Download references

Authors