DAMPs and PDT-mediated photo-oxidative stress: exploring the unknown
Abhishek D Garg1, Dmitri V Krysko, Peter Vandenabeele
1Department of Molecular Cell Biology, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium.
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.
Insights
Damage-associated molecular patterns (DAMPs) are released by dying cancer cells, activating the immune system. Photodynamic therapy (PDT) effectively utilizes DAMPs to stimulate anti-tumor immunity and control residual disease.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Damage-associated molecular patterns (DAMPs) are endogenous molecules released by dying cells.
- DAMPs activate antigen-presenting cells (APCs), stimulating innate and adaptive immunity.
- Cancer cells dying from certain therapies expose DAMPs crucial for anti-tumor immune responses.
Purpose of the Study:
- To review mechanisms of DAMP exposure and release during cell death.
- To explore the immunological consequences of DAMPs in cancer therapy.
- To discuss how photodynamic therapy (PDT) utilizes DAMPs to stimulate anti-tumor immunity.
Main Methods:
- Literature review on DAMPs, cell death mechanisms, and immunological consequences.
- Analysis of DAMP exposure and release signaling pathways.
- Discussion of PDT-induced DAMPs and their role in anti-tumor immune responses.
Main Results:
- Dying cancer cells release specific DAMPs that activate anti-tumor immunity.
- PDT induces oxidative stress, leading to DAMP exposure and release.
- PDT-generated DAMPs are vital for stimulating host immune responses against residual cancer.
Conclusions:
- PDT is a unique cancer therapy that combines tumor cell destruction with immune stimulation via DAMPs.
- Understanding DAMPs in PDT can lead to optimized cancer immunotherapies.
- Further research may identify novel DAMPs for enhanced anti-tumor immune responses.
