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The Role Of Phagocytosis In Cell Deaths By Photodynamic Therapy pp. 51-92 $100.00
Authors:  (E. Panzarini, V. Inguscio and L. Dini, Department of Biological and Environmental Science and Technology (Di.S.Te.B.A.), University of Salento, Italy)
Abstract:
Resistance to cell death and the ability to overrule immunosurveillance represent two hallmarks of tumour cells. The optimal cancer treatment should combine the induction of cell death and immunostimulatory effects based on immune cells activation consequent to the immunogenic characteristics of dead cells and their removal.
The dynamic interplay between dead cell and phagocytes leading to efficient phagocytosis is divided in four steps: 1) attraction and accumulation of phagocytes to the site of apoptotic cells, 2) recognition and tethering, 3) internalization and 4) processing of dead cells within the phagocytes avoiding phlogosis. Apoptotic cells secrete chemotactic signals attracting phagocytes and expose on plasma membrane ligands mediating receptor-specific physical contact with phagocytes. Indeed, the subsequent internalization steps and outcomes, i.e. immunotolerance or immunomodulation, profoundly depend on the phagocytic receptors involved.
PhotoDynamic Therapy (PDT), a promising new cancer treatment, is based on the synergic action of photosensitizing drugs (PS) and light irradiation that allow to kill the cells respectively via chemical and physical stress. Highly Reactive Oxygen Species (ROS), formed by the transfer of energy absorbed by PS upon irradiation to molecular oxygen, mediate the destruction of target cells. The best feature of PDT is the ROS damage directionality, depending on PS localization that in turn is mediated by its hydrophilicity/hydrophobicity, and the precise delivery of light to the treated sites. Multiple advantages characterize PDT as cancer treatment modality and make it potentially capable to meet many currently unmet medical needs. Particularly, PDT elicits a strong acute inflammation, orchestrated by both the innate and adaptive immune system, ensuring a protective effect by containing the disruption of tissue homeostasis and removal of damaged cells. The acute inflammatory response depends on photosensitized dead cells. Indeed, PDT not only induces apoptosis, autophagy and necrosis in the tumour cells, but it is also effective to rapidly generate an abundance of alarm/danger signals, called Damage-Associated Molecular Patterns (DAMPs), detected by the innate immunity alert elements. These, recruited to the sites of dead cells, eliminate injured and dead cells by phagocytosis and trigger the antitumour immunity by maturation and activation of dendritic cells (DCs).
Here we will discuss whether the multiple PDT-induced cell death types can result in an immune response, linked to the exposure and/or release of signals by dying cells, ending in the phagocytosis by the immune cells. 


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The Role Of Phagocytosis In Cell Deaths By Photodynamic Therapy pp. 51-92