Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death
Theocharis Panaretakis,Theocharis Panaretakis,Theocharis Panaretakis,Oliver Kepp,Oliver Kepp,Oliver Kepp,Ulf Brockmeier,Antoine Tesniere,Antoine Tesniere,Antoine Tesniere,Ann Charlotte Björklund,Daniel C. Chapman,Michael Durchschlag,Nicholas Joza,Nicholas Joza,Nicholas Joza,Gérard Pierron,Peter van Endert,Peter van Endert,Junying Yuan,Laurence Zitvogel,Laurence Zitvogel,Frank Madeo,David B. Williams,Guido Kroemer,Guido Kroemer,Guido Kroemer +26 more
TLDR
Depletion of PERK, caspase‐8 or SNAREs had no effect on cell death induced by anthracyclines, yet abolished the immunogenicity of cell death, which could be restored by absorbing recombinant CRT to the cell surface.Abstract:
Dying tumour cells can elicit a potent anticancer immune response by exposing the calreticulin (CRT)/ERp57 complex on the cell surface before the cells manifest any signs of apoptosis. Here, we enumerate elements of the pathway that mediates pre-apoptotic CRT/ERp57 exposure in response to several immunogenic anticancer agents. Early activation of the endoplasmic reticulum (ER)-sessile kinase PERK leads to phosphorylation of the translation initiation factor eIF2α, followed by partial activation of caspase-8 (but not caspase-3), caspase-8-mediated cleavage of the ER protein BAP31 and conformational activation of Bax and Bak. Finally, a pool of CRT that has transited the Golgi apparatus is secreted by SNARE-dependent exocytosis. Knock-in mutation of eIF2α (to make it non-phosphorylatable) or BAP31 (to render it uncleavable), depletion of PERK, caspase-8, BAP31, Bax, Bak or SNAREs abolished CRT/ERp57 exposure induced by anthracyclines, oxaliplatin and ultraviolet C light. Depletion of PERK, caspase-8 or SNAREs had no effect on cell death induced by anthracyclines, yet abolished the immunogenicity of cell death, which could be restored by absorbing recombinant CRT to the cell surface.read more
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Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Lorenzo Galluzzi,Lorenzo Galluzzi,Ilio Vitale,Stuart A. Aaronson,John M. Abrams,Dieter Adam,Patrizia Agostinis,Emad S. Alnemri,Lucia Altucci,Ivano Amelio,David W. Andrews,David W. Andrews,Margherita Annicchiarico-Petruzzelli,Alexey V. Antonov,Eli Arama,Eric H. Baehrecke,Nickolai A. Barlev,Nicolas G. Bazan,Francesca Bernassola,Mathieu J.M. Bertrand,Katiuscia Bianchi,Mikhail V. Blagosklonny,Klas Blomgren,Christoph Borner,Patricia Boya,Catherine Brenner,Catherine Brenner,Michelangelo Campanella,Eleonora Candi,Didac Carmona-Gutierrez,Francesco Cecconi,Francis Ka-Ming Chan,Navdeep S. Chandel,Emily H. Cheng,Jerry E. Chipuk,John A. Cidlowski,Aaron Ciechanover,Gerald M. Cohen,Marcus Conrad,Juan R. Cubillos-Ruiz,Peter E. Czabotar,Peter E. Czabotar,Vincenzo D'Angiolella,Ted M. Dawson,Valina L. Dawson,Vincenzo De Laurenzi,Ruggero De Maria,Klaus-Michael Debatin,Ralph J. DeBerardinis,Mohanish Deshmukh,Nicola Di Daniele,Francesco Di Virgilio,Vishva M. Dixit,Scott J. Dixon,Colin S. Duckett,Brian David Dynlacht,Wafik S. El-Deiry,John W. Elrod,Gian Maria Fimia,Simone Fulda,Simone Fulda,Ana J. García-Sáez,Abhishek D. Garg,Carmen Garrido,Carmen Garrido,Evripidis Gavathiotis,Pierre Golstein,Eyal Gottlieb,Eyal Gottlieb,Douglas R. Green,Lloyd A. Greene,Hinrich Gronemeyer,Atan Gross,György Hajnóczky,J. Marie Hardwick,Isaac S. Harris,Michael O. Hengartner,Claudio Hetz,Hidenori Ichijo,Marja Jäättelä,Bertrand Joseph,Philipp J. Jost,Philippe Juin,William J. Kaiser,Michael Karin,Thomas Kaufmann,Oliver Kepp,Adi Kimchi,Richard N. Kitsis,Daniel J. Klionsky,Richard A. Knight,Sharad Kumar,Sam W. Lee,John J. Lemasters,Beth Levine,Andreas Linkermann,Stuart A. Lipton,Richard A. Lockshin,Richard A. Lockshin,Carlos López-Otín,Scott W. Lowe,Scott W. Lowe,Tom Luedde,Enrico Lugli,Marion MacFarlane,Frank Madeo,Michal Malewicz,Walter Malorni,Gwenola Manic,Jean-Christophe Marine,Seamus J. Martin,Jean-Claude Martinou,Jan Paul Medema,Patrick Mehlen,Pascal Meier,Sonia Melino,Edward A. Miao,Jeffery D. Molkentin,Ute M. Moll,Cristina Muñoz-Pinedo,Shigekazu Nagata,Gabriel Núñez,Andrew Oberst,Moshe Oren,Michael Overholtzer,Michele Pagano,Theocharis Panaretakis,Theocharis Panaretakis,Manolis Pasparakis,Josef M. Penninger,David M. Pereira,Shazib Pervaiz,Marcus E. Peter,Mauro Piacentini,Paolo Pinton,Jochen H. M. Prehn,Hamsa Puthalakath,Gabriel A. Rabinovich,Markus Rehm,Rosario Rizzuto,Cecília M. P. Rodrigues,David C. Rubinsztein,Thomas Rudel,Kevin M. Ryan,Emre Sayan,Luca Scorrano,Feng Shao,Yufang Shi,Yufang Shi,John Silke,John Silke,Hans-Uwe Simon,Antonella Sistigu,Brent R. Stockwell,Andreas Strasser,Gyorgy Szabadkai,Gyorgy Szabadkai,Gyorgy Szabadkai,Stephen W.G. Tait,Daolin Tang,Daolin Tang,Nektarios Tavernarakis,Andrew Thorburn,Yoshihide Tsujimoto,Boris Turk,Tom Vanden Berghe,Peter Vandenabeele,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Andreas Villunger,Herbert W. Virgin,Karen H. Vousden,Domagoj Vucic,Erwin F. Wagner,Henning Walczak,David Wallach,Ying Wang,James A. Wells,Will Wood,Junying Yuan,Zahra Zakeri,Boris Zhivotovsky,Boris Zhivotovsky,Laurence Zitvogel,Gerry Melino,Gerry Melino,Guido Kroemer +186 more
TL;DR: The Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
Journal ArticleDOI
Immunogenic Cell Death in Cancer Therapy
TL;DR: It is postulate that ICD constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies and its subversion by pathogens.
Journal ArticleDOI
Immunogenic cell death in cancer and infectious disease
TL;DR: Current knowledge on the mechanisms that underlie the activation of immune responses against dying cells and their pathophysiological relevance are reviewed.
Journal ArticleDOI
Immunogenic cell death and DAMPs in cancer therapy.
Dmitri V. Krysko,Abhishek D. Garg,Agnieszka Kaczmarek,Olga Krysko,Patrizia Agostinis,Peter Vandenabeele +5 more
TL;DR: The role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and the effect of therapy-resistant cancer microevolution on ICD are discussed.
Journal ArticleDOI
Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice.
Mickaël Michaud,Mickaël Michaud,Mickaël Michaud,Isabelle Martins,Isabelle Martins,Isabelle Martins,Abdul Qader Sukkurwala,Abdul Qader Sukkurwala,Abdul Qader Sukkurwala,Sandy Adjemian,Sandy Adjemian,Sandy Adjemian,Yuting Ma,Patrizia Pellegatti,Shensi Shen,Shensi Shen,Shensi Shen,Oliver Kepp,Oliver Kepp,Oliver Kepp,Marie Scoazec,Grégoire Mignot,Santiago Rello-Varona,Santiago Rello-Varona,Santiago Rello-Varona,Maximilien Tailler,Maximilien Tailler,Maximilien Tailler,Laurie Menger,Laurie Menger,Laurie Menger,Erika Vacchelli,Erika Vacchelli,Erika Vacchelli,Lorenzo Galluzzi,Lorenzo Galluzzi,Lorenzo Galluzzi,François Ghiringhelli,Francesco Di Virgilio,Laurence Zitvogel,Guido Kroemer +40 more
TL;DR: It is demonstrated that autophagy, which is often disabled in cancer, is dispensable for chemotherapy-induced cell death but required for its immunogenicity, and increased extracellular ATP concentrations improve the efficacy of antineoplastic chemotherapies when Autophagy is disabled.
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Calreticulin exposure dictates the immunogenicity of cancer cell death
Michel Obeid,Antoine Tesniere,Antoine Tesniere,Antoine Tesniere,François Ghiringhelli,François Ghiringhelli,François Ghiringhelli,Gian Maria Fimia,Lionel Apetoh,Lionel Apetoh,Lionel Apetoh,Jean-Luc Perfettini,Jean-Luc Perfettini,Jean-Luc Perfettini,Maria Castedo,Maria Castedo,Maria Castedo,Grégoire Mignot,Grégoire Mignot,Grégoire Mignot,Theoharis Panaretakis,Theoharis Panaretakis,Theoharis Panaretakis,Noelia Casares,Noelia Casares,Noelia Casares,Didier Métivier,Didier Métivier,Didier Métivier,Nathanael Larochette,Nathanael Larochette,Nathanael Larochette,Peter van Endert,Peter van Endert,Fabiola Ciccosanti,Mauro Piacentini,Laurence Zitvogel,Laurence Zitvogel,Laurence Zitvogel,Guido Kroemer,Guido Kroemer,Guido Kroemer +41 more
TL;DR: It is shown that anthracyclin-induced CRT translocation induces the rapid, preapoptotic translocation of calreticulin (CRT) to the cell surface and is identified as a key feature determining anticancer immune responses.
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