Macrophages hijack anti-pd-1 therapy

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 Access Nature and 54 other Nature

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calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support 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 * David Killock View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Killock, D. Macrophages hijack anti-PD-1 therapy. _Nat Rev Clin Oncol_ 14, 394 (2017). https://doi.org/10.1038/nrclinonc.2017.79 Download citation * Published: 31 May 2017 * Issue

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