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Consensus guidelines for the detection of immunogenic cell death

(2014) ONCOIMMUNOLOGY. 3(9).
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Abstract
Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.
Keywords
HMGB1, endoplasmic reticulum stress, calreticulin, ATP release, autophagy, immunotherapy, MITOCHONDRIAL-MEMBRANE PERMEABILIZATION, HEAT-SHOCK PROTEINS, GROUP BOX-1 PROTEIN, APOPTOTIC CALRETICULIN EXPOSURE, MOLECULAR-PATTERN MOLECULES, ANTICANCER IMMUNE-RESPONSES, FLOW-CYTOMETRIC DETECTION, HUMAN TUMOR-CELLS, FIND-ME SIGNAL, NECROTIC CELLS

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Citation

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Chicago
Kepp, Oliver, Laura Senovilla, Ilio Vitale, Erika Vacchelli, Sandy Adjemian, Patrizia Agostinis, Lionel Apetoh, et al. 2014. “Consensus Guidelines for the Detection of Immunogenic Cell Death.” Oncoimmunology 3 (9).
APA
Kepp, O., Senovilla, L., Vitale, I., Vacchelli, E., Adjemian, S., Agostinis, P., Apetoh, L., et al. (2014). Consensus guidelines for the detection of immunogenic cell death. ONCOIMMUNOLOGY, 3(9).
Vancouver
1.
Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, et al. Consensus guidelines for the detection of immunogenic cell death. ONCOIMMUNOLOGY. 2014;3(9).
MLA
Kepp, Oliver, Laura Senovilla, Ilio Vitale, et al. “Consensus Guidelines for the Detection of Immunogenic Cell Death.” ONCOIMMUNOLOGY 3.9 (2014): n. pag. Print.
@article{5894845,
  abstract     = {Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named {\textacutedbl}immunogenic cell death{\textacutedbl} (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.},
  articleno    = {e955691},
  author       = {Kepp, Oliver and Senovilla, Laura and Vitale, Ilio and Vacchelli, Erika and Adjemian, Sandy and Agostinis, Patrizia and Apetoh, Lionel and Aranda, Fernando and Barnaba, Vincenzo and Bloy, Norma and Bracci, Laura and Breckpot, Karine and Brough, David and Buqu{\'e}, Aitziber and Castro, Maria G and Cirone, Mara and Colombo, Maria I and Cremer, Isabelle and Demaria, Sandra and Dini, Luciana and Eliopoulos, Aristides G and Faggioni, Alberto and Formenti, Silvia C and Fu\v{c}{\'i}kov{\'a}, Jitka and Gabriele, Lucia and Gaipl, Udo S and Galon, J{\'e}r{\^o}me and Garg, Abhishek and Ghiringhelli, Fran\c{c}ois and Giese, Nathalia A and Guo, Zong Sheng and Hemminki, Akseli and Herrmann, Martin and Hodge, James W and Holdenrieder, Stefan and Honeychurch, Jamie and Hu, Hong-Min and Huang, Xing and Illidge, Tim M and Kono, Kodji and Korbelik, Mladen and Krysko, Dmitri and Loi, Sherene and Lowenstein, Pedro R and Lugli, Enrico and Ma, Yuting and Madeo, Frank and Manfredi, Angelo A and Martins, Isabelle and Mavilio, Domenico and Menger, Laurie and Merendino, Nicol{\`o} and Michaud, Michael and Mignot, Gregoire and Mossman, Karen L and Multhoff, Gabriele and Oehler, Rudolf and Palombo, Fabio and Panaretakis, Theocharis and Pol, Jonathan and Proietti, Enrico and Ricci, Jean-Ehrland and Riganti, Chiara and Rovere-Querini, Patrizia and Rubartelli, Anna and Sistigu, Antonella and Smyth, Mark J and Sonnemann, Juergen and Spisek, Radek and Stagg, John and Sukkurwala, Abdul Qader and Tartour, Eric and Thorburn, Andrew and Thorne, Stephen H and Vandenabeele, Peter and Velotti, Francesca and Workenhe, Samuel T and Yang, Haining and Zong, Wei-Xing and Zitvogel, Laurence and Kroemer, Guido and Galluzzi, Lorenzo},
  issn         = {2162-4011},
  journal      = {ONCOIMMUNOLOGY},
  language     = {eng},
  number       = {9},
  pages        = {19},
  title        = {Consensus guidelines for the detection of immunogenic cell death},
  url          = {http://dx.doi.org/10.4161/21624011.2014.955691},
  volume       = {3},
  year         = {2014},
}

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