PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Mouse and human tumour-associated macrophages express PD-1, which increases with cancer stage and induces decreased phagocytosis by macrophages; by contrast, PD-L1 removal increases phagocytosis in vivo , decreases tumour burden and increases survival of mice. Blocking tumour immunity Therapeutic an...
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Published in | Nature (London) Vol. 545; no. 7655; pp. 495 - 499 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
25.05.2017
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Mouse and human tumour-associated macrophages express PD-1, which increases with cancer stage and induces decreased phagocytosis by macrophages; by contrast, PD-L1 removal increases phagocytosis
in vivo
, decreases tumour burden and increases survival of mice.
Blocking tumour immunity
Therapeutic antibodies that inhibit the interaction of programmed cell death protein (PD-1) with its ligand (PD-L1) are known to activate cytotoxic T cells. Here Irv Weissmann and colleagues study the role for PD-1 on tumour-infiltrating macrophages in mice. The study shows that PD-1-expressing macrophages have limited phagocytic capabilities and that blocking PD-1/PD-L1 enhances phagocytosis and correlates with reduced tumour growth. This finding suggests a T-cell-independent mechanism of therapeutic activity of PD-1/PD-L1 inhibitors which may be clinically relevant.
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance
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,
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. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system
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,
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. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin’s lymphoma
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,
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,
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,
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,
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. Although it is well established that PD-1–PD-L1 blockade activates T cells, little is known about the role that this pathway may have in tumour-associated macrophages (TAMs). Here we show that both mouse and human TAMs express PD-1. TAM PD-1 expression increases over time in mouse models of cancer and with increasing disease stage in primary human cancers. TAM PD-1 expression correlates negatively with phagocytic potency against tumour cells, and blockade of PD-1–PD-L1
in vivo
increases macrophage phagocytosis, reduces tumour growth and lengthens the survival of mice in mouse models of cancer in a macrophage-dependent fashion. This suggests that PD-1–PD-L1 therapies may also function through a direct effect on macrophages, with substantial implications for the treatment of cancer with these agents. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Correspondence and requests for materials should be addressed to I.L.W. (irv@stanford.edu). |
ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/nature22396 |