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The parallel lives of angiogenesis and immunosuppression: cancer and other tales

Nature Reviews Immunology volume 11, pages 702–711 (2011)Cite this article

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Abstract

Emerging evidence indicates that angiogenesis and immunosuppression frequently occur simultaneously in response to diverse stimuli. Here, we describe a fundamental biological programme that involves the activation of both angiogenesis and immunosuppressive responses, often through the same cell types or soluble factors. We suggest that the initiation of these responses is part of a physiological and homeostatic tissue repair programme, which can be co-opted in pathological states, notably by tumours. This view can help to devise new cancer therapies and may have implications for aseptic tissue injury, pathogen-mediated tissue destruction, chronic inflammation and even reproduction.

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Figure 1: Promotion of angiogenesis by immunosuppressive cells.
Figure 2: The role of VEGFA in immune suppression.
Figure 3: Modulation of immune cell recruitment and diapedesis through the endothelial barrier by the tumour microenvironment.
Figure 4: Direct immune regulation by the endothelium.

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Acknowledgements

The authors are supported by US National Institutes of Health grant R01-CA116779, US National Cancer Institute ovarian cancer SPORE grant P01-CA83638 and the Ovarian Cancer Research Fund.

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  1. Gregory T. Motz and George Coukos are at the Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.,

    Gregory T. Motz & George Coukos

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Correspondence to George Coukos.

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Glossary

Adoptive cell therapy

Very simply, the transfusion of lymphocytes into patients for the treatment of cancer. Strategies that have enjoyed success include the rapid ex vivo expansion of tumour-infiltrating lymphocytes followed by autologous reinjection. Engineering of patient peripheral blood T cells to express artificial T cell receptors or chimeric antigen receptors that recognize tumour antigens is a recently developed strategy that has proved successful.

Diapedesis

Leukocyte migration through the endothelium that is mediated by leukocyte-secreted proteases that disrupt the endothelial cell barrier.

Extravasation

The multistep process of leukocyte infiltration through the endothelium. This process proceeds through the stages of leukocyte rolling, adhesion, diapedesis and finally migration to the surrounding tissues.

Ischaemia–reperfusion injury

Disruption of proper blood flow, either experimentally or otherwise, followed by restoration of normal blood flow results in significant hypoxia, tissue damage and inflammation followed by angiogenesis and immunosuppression.

Mural cells

Cells that physically surround the endothelial cells of blood vessels. This population is comprised of vascular smooth muscle cells (associated with veins and arteries) and pericytes (associated with capillaries and developing vessels).

Pericyte

A mural cell that is thought to have significant roles in supporting the growth and survival of endothelial cells during angiogenesis, particularly in tumours.

Trogocytosis

Following the formation of the immunological synapse, membrane fragments from the antigen-presenting cell are physically transferred to, and transiently incorporated in, the membrane of the interacting T cell (or B or NK cell). The biological significance remains wholly unknown.

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Motz, G., Coukos, G. The parallel lives of angiogenesis and immunosuppression: cancer and other tales. Nat Rev Immunol 11, 702–711 (2011). https://doi.org/10.1038/nri3064

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