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DAMPs and PDT-mediated photo-oxidative stress: exploring the unknown

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Abstract

Damage-associated molecular patterns (DAMPs) or cell death associated molecular patterns (CDAMPs) are a subset of endogenous intracellular molecules that are normally hidden within living cells but become either passively released by primary and secondary necrotic cells or actively exposed and secreted by the dying cells. Once released, DAMPs are sensed by the innate immune system and act as activators of antigen-presenting cells (APCs) to stimulate innate and adaptive immunity. Cancer cells dying in response to a subset of conventional anticancer modalities exhibit a particular composition of DAMPs at their cell surface, which has been recently shown to be vital for the stimulation of the host immune system and the control of residual disease. Photodynamic therapy (PDT) for cancer has long been shown to be capable of killing malignant cells and concomitantly stimulate the host immune system, properties that are likely linked to its ability of inducing exposure/release of certain DAMPs. PDT, by evoking oxidative stress at specific subcellular sites through the light activation of organelle-associated photosensitizers, may be unique in incorporating tumour cells destruction and antitumor immune response in one therapeutic paradigm. Here we review the current knowledge about mechanisms and signalling cascades leading to the exposure of DAMPs at the cell surface or promoting their release, the cell death mechanism associated to these processes and its immunological consequences.We also discuss how certain PDT paradigms may yield therapies that optimally stimulate the immune system and lead to the discovery of new DAMPs.

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Authors and Affiliations

  1. Department of Molecular Cell Biology, Faculty of Medicine, Catholic University of Leuven, Campus Gasthuisberg ON1, Herestraat 49, B-3000, Leuven, Belgium

    Abhishek D. Garg & Patrizia Agostinis

  2. Department for Molecular Biomedical Research, VIB, Molecular Signalling and Cell Death Unit, Belgium

    Dmitri V. Krysko & Peter Vandenabeele

  3. Department of Biomedical Molecular Biology, Ghent University, Belgium

    Dmitri V. Krysko & Peter Vandenabeele

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  1. Abhishek D. Garg
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Correspondence to Patrizia Agostinis.

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This article is published as part of a themed issue on immunological aspects and drug delivery technologies in PDT.

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Garg, A.D., Krysko, D.V., Vandenabeele, P. et al. DAMPs and PDT-mediated photo-oxidative stress: exploring the unknown. Photochem Photobiol Sci 10, 670–680 (2011). https://doi.org/10.1039/c0pp00294a

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