Consensus guidelines for the detection of immunogenic cell death

Oliver Kepp, Laura Senovilla, Ilio Vitale, Erika Vacchelli, Sandy Adjemian, Patrizia Agostinis, Lionel Apetoh, Fernando Aranda, Vincenzo Barnaba, Norma Bloy, Laura Bracci, Karine Breckpot, David Brough, Aitziber Buqué, Maria G. Castro, Mara Cirone, Maria I. Colombo, Isabelle Cremer, Sandra Demaria, Luciana DiniAristides G. Eliopoulos, Alberto Faggioni, Silvia C. Formenti, Jitka Fučíková, Lucia Gabriele, Udo S. Gaipl, Jérôme Galon, Abhishek Garg, François Ghiringhelli, Nathalia A. Giese, Zong Sheng Guo, Akseli Hemminki, Martin Herrmann, James W. Hodge, Stefan Holdenrieder, Jamie Honeychurch, Hong Min Hu, Xing Huang, Tim M. Illidge, Koji Kono, Mladen Korbelik, Dmitri V. Krysko, Sherene Loi, Pedro R. Lowenstein, Enrico Lugli, Yuting Ma, Frank Madeo, Angelo A. Manfredi, Isabelle Martins, Domenico Mavilio, Laurie Menger, Nicolò Merendino, Michael Michaud, Gregoire Mignot, Karen L. Mossman, Gabriele Multhoff, Rudolf Oehler, Fabio Palombo, Theocharis Panaretakis, Jonathan Pol, Enrico Proietti, Jean Ehrland Ricci, Chiara Riganti, Patrizia Rovere-Querini, Anna Rubartelli, Antonella Sistigu, Mark J. Smyth, Juergen Sonnemann, Radek Spisek, John Stagg, Abdul Qader Sukkurwala, Eric Tartour, Andrew Thorburn, Stephen H. Thorne, Peter Vandenabeele, Francesca Velotti, Samuel T. Workenhe, Haining Yang, Wei Xing Zong, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere955691
JournalOncoImmunology
Volume3
Issue number9
DOIs
Publication statusPublished - Oct 1 2014

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Keywords

  • ATP release
  • Autophagy
  • Calreticulin
  • Endoplasmic reticulum stress
  • HMGB1
  • Immunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

Kepp, O., Senovilla, L., Vitale, I., Vacchelli, E., Adjemian, S., Agostinis, P., Apetoh, L., Aranda, F., Barnaba, V., Bloy, N., Bracci, L., Breckpot, K., Brough, D., Buqué, A., Castro, M. G., Cirone, M., Colombo, M. I., Cremer, I., Demaria, S., ... Galluzzi, L. (2014). Consensus guidelines for the detection of immunogenic cell death. OncoImmunology, 3(9), [e955691]. https://doi.org/10.4161/21624011.2014.955691