2016
DOI: 10.1038/cdd.2016.5
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Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation

Abstract: Phagocytosis of dying cells is a major homeostatic process that represents the final stage of cell death in a tissue context. Under basal conditions, in a diseased tissue (such as cancer) or after treatment with cytotoxic therapies (such as anticancer therapies), phagocytosis has a major role in avoiding toxic accumulation of cellular corpses. Recognition and phagocytosis of dying cancer cells dictate the eventual immunological consequences (i.e., tolerogenic, inflammatory or immunogenic) depending on a series… Show more

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Cited by 115 publications
(105 citation statements)
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References 159 publications
(248 reference statements)
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“…1 However, meanwhile it is well accepted that immune mechanisms contribute to the therapeutic outcome and that the mode of tumor cell death determines if and to which extent irradiation converts the tumor into an in situ vaccine. 24 Apart from tumor antigens which need to be made accessible to the immune system, the presence of adjuvants orchestrating the recruitment, differentiation, and activation of antigen-presenting cells (APCs) in the tumor microenvironment is of pivotal importance for the successful priming of anti-tumor immunity. 5,6 In this regard, tumor cells undergoing immunogenic forms of cell death are known to release damage-associated molecular patterns (DAMPs), including heat shock protein 70 (HSP70), high mobility group box1 (HMGB1), and ATP, thereby supporting the recruitment and maturation of APCs.…”
Section: Introductionmentioning
confidence: 99%
“…1 However, meanwhile it is well accepted that immune mechanisms contribute to the therapeutic outcome and that the mode of tumor cell death determines if and to which extent irradiation converts the tumor into an in situ vaccine. 24 Apart from tumor antigens which need to be made accessible to the immune system, the presence of adjuvants orchestrating the recruitment, differentiation, and activation of antigen-presenting cells (APCs) in the tumor microenvironment is of pivotal importance for the successful priming of anti-tumor immunity. 5,6 In this regard, tumor cells undergoing immunogenic forms of cell death are known to release damage-associated molecular patterns (DAMPs), including heat shock protein 70 (HSP70), high mobility group box1 (HMGB1), and ATP, thereby supporting the recruitment and maturation of APCs.…”
Section: Introductionmentioning
confidence: 99%
“…Immune responses against dead-cell antigen result from a combination of antigenicity and adjuvanticity provided by DAMPs. [4][5][6] As an overarching leitmotif, cell death hence has major consequences for normal tissue homeostasis, stress responses, inflammation and antimicrobial as well as anticancer immune responses, as this is clearly illustrated in this special issue of Cell Death & Differentiation. How can we link cell death then to pathophysiology?…”
mentioning
confidence: 99%
“…5 Nonetheless, the simple equation that apoptosis would be an anti-inflammatory and nonimmunogenic event, contrasting with necrosis that would be proinflammatory and potentially immunogenic, constitutes a hitherto inadmissible oversimplification. 6,11,12 At a second level, the surface exposure and release of a vast collection of cell danger-associated molecular patterns (CDAMPs) shape the response to stressed, dying and dead cells. Such CDAMPs include an ever-expanding list of 'findme' signals (also called chemotactic signals) that attract specific leukocyte populations, 13 'keep-out' signals (also called chemorepellents) that repel other leukocyte types, 'eatme' signals that stimulate phagocytosis in different ways, 14,15 'don't eat me' signals that avoid phagocytosis 15 and a collection of DAMPs that are often proteins or nucleic acids, which can only be fully released if the plasma membrane bursts, 6,11,12 as well as anti-inflammatory factors that mitigate local tissue reactions.…”
mentioning
confidence: 99%
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