Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy |
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Authors: | Oliver Kepp Lorenzo Galluzzi Isabelle Martins Frederic Schlemmer Sandy Adjemian Mickael Michaud Abdul Qader Sukkurwala Laurie Menger Laurence Zitvogel " target="_blank">Guido Kroemer |
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Institution: | 1.INSERM, U848, Institut Gustave Roussy, Pavillon de Recherche 1,Villejuif (Paris),France;2.Institut Gustave Roussy,Villejuif,France;3.Université Paris Sud, Paris 11,Villejuif,France;4.INSERM, U1015, and CICBT507,Villejuif,France;5.Metabolomics Platform, Institut Gustave Roussy,Villejuif,France;6.Centre de Recherche des Cordeliers,Paris,France;7.P?le de Biologie, H?pital Européen Georges Pompidou, AP-HP,Paris,France;8.Université Paris Descartes, Paris 5,Paris,France |
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Abstract: | The success of some chemo- and radiotherapeutic regimens relies on the induction of immunogenic tumor cell death and on the
induction of an anticancer immune response. Cells succumbing to immunogenic cell death undergo specific changes in their surface
characteristics and release pro-immunogenic factors according to a defined spatiotemporal pattern. This stimulates antigen
presenting cells such as dendritic cells to efficiently take up tumor antigens, process them, and cross-prime cytotoxic T
lymphocytes, thus eliciting a tumor-specific cognate immune response. Such a response can also target therapy-resistant tumor
(stem) cells, thereby leading, at least in some instances, to tumor eradication. In this review, we shed some light on the
molecular identity of the factors that are required for cell death to be perceived as immunogenic. We discuss the intriguing
observations that the most abundant endoplasmic reticulum protein, calreticulin, the most abundant intracellular metabolite,
ATP, and the most abundant non-histone chromatin-binding protein, HMGB1, can determine whether cell death is immunogenic as
they appear on the surface or in the microenvironment of dying cells. |
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